General News

7-31-08 – CRC Screening Rates Remain Low in Europe, Australia and the US

A recently released report summarized on this website showed low CRC screening rates among Asians. Now 2 more reports have been published showing similarly low screening in Europe, Australia and the United States.

The first international report on colon cancer screening in Europe and Australia was released in late June by the London School of Economics (LSE), confirming that few countries have prioritized CRC screening and treatment.

Lead author Panos Kanavos, senior lecturer at LSE, states the report identifies the following problems:

Poor data collection from cancer registries
Limited public and political awareness of CRC
Few formal screening programs
Variable treatment guidelines
Poor or delayed access to treatment
Slow adoption of new technologies (surgery, targeted anti-cancer drugs)

The report urges prioritization of screening and treatment of CRC through greater pan-European cooperation and delivery of an integrated prevention program.
Traditional barriers (socioeconomic factors, language barriers) don’t explain the disparity among Asians

Just 50% of Americans who should be screened for CRC are actually getting tested, and lack of health insurance appears to be a major reason, new research suggests. Regular screening for CRC is recommended for people aged 50 and older, but screening rates are known to be low, Dr Jean Shapiro and her colleagues note in the July 2008 issue of Cancer Epidemiology, Biomarkers and Prevention.

The study analyzed data on 13,269 people aged 50 and older who participated in the 2005 National Health Interview Survey.
Exactly half of the survey respondents said they had been screened for CRC with a fecal occult blood test (FOBT) in the past year, endoscopy within the past 10 years, or both.
Only 24.1% of people who had no health insurance had gotten tested. Among people who reported having no usual source of health care, 24.7% had been screened.
37% of people who had not finished high school had been screened, while 60.7% of college graduates had.
Among people with household incomes of $20,000 or less, 37.4% had been screened, compared to 58.5% of those with incomes of $75,000 or more. Just 19.5% of people who had not seen a doctor in the past year had been screened.
Roughly 50% of survey respondents who failed to get screened said they had "never thought about it," while 20% said their doctor "did not order it."
Conclusions of the researchers:

More people need to be informed about CRC screening
Doctors and nurses must do a better job of telling their patients about testing
More people should have health insurance coverage in the US

Individuals without health coverage can call 1 (800) 4-CANCER or 1 (800) ACS-2345 to find out about low-cost screening options in their community, or check with their local department of health. More information on colorectal cancer screening is available at the CDC's Web site at www.cdc.gov/screenforlife.

A link to the abstract is available at http://cebp.aacrjournals.org/cgi/content/abstract/17/7/1623

7-18-08 – Asians Are Less Likely To Undergo CRC Screening

A paper in the June 23, 2008 issue of Archives of Internal Medicine reports that Asians are less likely than non-Hispanic whites and other racial or ethnic minorities to undergo CRC screening. Dr Anthony F. Jerant and colleagues analyzed screening behavior data using linked data from 22,973 respondents to the 2001-2005 Medical Expenditure Panel Survey and the 2000-2004 National Health Interview Survey for respondents = age 50 from four major US racial/ethnic categories (non-Hispanic white, black, Hispanic, Asian). In general, they found:

Women were less likely to be screened than men
Minority populations have lower screening rates compares with whites
Traditional barriers (socioeconomic factors, language barriers) don’t explain the disparity among Asians

In this study by Jerant, et al., minorities reported lower rates compared with whites for all measures of screening. The largest differences involved Asians, who were 60% less likely than whites to have combined screening (fecal occult blood test [FOBT] + endoscopic exam) and 59% less likely to have endoscopy. In the fully adjusted analysis, all differences between Hispanics and non-Hispanic whites disappeared and black/non-Hispanic white differences remained only for FOBT (with black participants having a higher FOBT screening rate). Significant differences between Asians and non-Hispanic whites persisted for all forms of screening.

The researchers state that whereas socioeconomic, access, and language barriers seem to drive the CRC screening disparities experienced by blacks and Hispanics, additional factors may exacerbate the disparities experienced by Asians and suggest that federal public health and research initiatives aimed at screening uptake in Asians should be implemented to complement those targeted to other ethnic groups.

Reference

Jerant AF, Fenton JJ, Franks P. Determinants of racial/ethnic colorectal cancer screening disparities. Arch Intern Med. 2008;168:1317-1324. A link to the abstract can be found at http://archinte.ama-assn.org/cgi/content/abstract/168/12/1317

06-26-08 – Predictive Biomarkers in The Treatment of mCRC

Individualizing treatment approaches for various cancers is gaining interest. Clinicians can use biomarkers to help determine appropriate treatment. These biomarkers can correlate with patient outcomes (survival or progression) and are thought of as either prognostic or predictive.¹ Although prognostic biomarkers are important, they do not predict whether the patient outcome will be improved by therapy with specific agents, limiting their effect on choices of therapy. If biomarkers could determine whether the outcome of a particular patient will be improved by treatment, unnecessary toxicity and costs associated with specific therapies could be avoided.

The importance of biomarkers is being utilized with the identification of KRAS as a predictor of response to epidermal growth factor inhibitor therapy. Recent clinical trials have determined that patients with mutation of KRAS essentially become non-responders to treatment with cetuximab and panitumumab.² Therefore, there is intense interest in predictive biomarkers to correlate the importance of particular therapies and patient outcome.

The Fluorouracil, Oxaliplatin, CPT-11: Use and Sequencing trial (FOCUS) is the largest randomized trial reported in metastatic colorectal cancer (mCRC) and includes a prospectively planned predictive biomarker study to help determine appropriate predictive markers for both irinotecan and oxaliplatin. The first results were recently published, which evaluates eleven biomarkers previously proposed in smaller studies.¹ The FOCUS trial determined

The effect of fluorouracil alone compared with fluorouracil and irinotecan, and with fluorouracil and oxaliplatin
The trial also evaluated candidate predictive biomarkers for irinotecan and oxaliplatin in 1,628 patients
The candidate biomarkers were tumor immunohistchemistry (IHC) for

MLH1/MSH2, p53, topoisomerase-1 (Topo1) and excision repair cross-complementing gene 1 (ERCC1), among others
Of the initially screened biomarkers, two (Topo-1 and MLH1/MSH2) were determined to be appropriate for analysis in the full population of patients
The primary end points were progression-free survival (PFS) and overall survival (OS)

The results showed:

1,313 patients (81%) were assessable for Topo1 IHC
In patients with low Topo1, PFS was not improved by the addition of either irinotecan or oxaliplatin
Patients with moderate/high Topo1 benefited from the addition of either drug (P = .005 OS, with P = .001 for irinotecan and P = .05 for oxaliplatin
Patients with high Topo1 had a major OS benefit with first-line combination chemotherapy, corresponding to a median survival advantage
MLH1.MSH2 did not show a significant interaction with treatment, but the low rate (4%) of loss limited the power of the study for the biomarker

The researchers concluded that Topo1 IHC did identify subpopulations of patients that did nor did not benefit from commonly used chemotherapy agents for mCRC (irinotecan and possibly oxaliplatin) and stated that if verified independently, this information could continue the individualization of therapy approaches to patients with this tumor type.²

References

Braun MS, Richman SD, Quirke P, et al. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS Trial. J Clin Oncol. 2008; 26:2690-2698. Abstract available at http://jco.ascopubs.org/cgi/content/abstract/26/16/2690. Accessed June 10, 2008.
Amado RG, Wolf M, Peeters M, et al. Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol. 2008;26:1626-1634. Abstract available at http://jco.ascopubs.org/cgi/content/abstract/26/10/1626. Accessed June 10, 2008.

5-23-08 – New Multi-Organization CRC Screening Guidelines Published

In the May/June 2008 issue of CA: A Cancer Journal for Clinicians (American Cancer Society), Levin and colleagues published screening and surveillance guidelines for the early detection of colorectal cancer (CRC) and adenomatous polyps. The authors represent the American Cancer Society Colorectal Cancer Advisory Group, the US Multi-Society Task Force and the American College of Radiology Colon Cancer Committee. This article updates each organization's guidelines according to current evidence. Screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy.

Screening tests fall into 2 general categories

Stool tests – best suited for the detection of cancer, although they also may provide positive findings for some advanced adenomas

Fecal occult blood test (FOBT)
Exfoliated DNA

Structural exams – detect adenocarcinoma as well as identify adenomatous polyps

Flexible sigmoidoscopy (FSIG)
Colonoscopy
Double-contrast barium enema (DCBE)
Computed tomographic colonography (CTC)

The authors recommend that, when possible, clinicians should make patients aware of the full range of screening options. At the very least, patients should be offered a choice between a (1) screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps and a (2) screening test that is primarily effective at early cancer detection. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.

Reference

Levin B, Liberman DA, McFarland B, et al. Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130-160.
Free full text access is available online at http://caonline.amcancersoc.org/cgi/content/full/58/3/130

5-14-08 – Colorectal Cancer in the Elderly

Colorectal cancer (CRC), a commonly occurring cancer and leading cause of death for both sexes, frequently occurs in patients of older age. The median age at diagnosis is 70 with many patients older than 70 when initially diagnosed with colon cancer¹ The overall survival (OS) for patients with metastatic CRC (mCRC) has been significantly prolonged, with many patients surviving over 24 months with this disease.

Kohne et al² point out, in their recently published paper in The Oncologist, that much of the research regarding potential treatments for CRC does not include results from the study of older patients, hampering clinicians to determine appropriate treatment regimens for this population. They further discuss the lack of participation of the elderly in key clinical trials and make suggestions on ways to include this important patient population. The authors point out that:

Survey data suggest that most (>70%) of elderly patients diagnosed with cancer are willing to be treated with strong, palliative chemotherapy
The elderly are not a homogenous population and contain individuals of differing overall health, independence, and performance status (PS)
The use of a comprehensive geriatric assessment is recommended to identify appropriate patients for therapy
Palliation is an important part of therapy for frail and elderly patients or those with a short life expectancy

The authors suggest that chronological age alone is not adequate enough to determine elderly patients who should receive chemotherapy treatments. Overall health, independence, and PS are more clinically relevant in determining not only ability to receive treatment, but in some studies reflected longer OS in patients receiving irinotecan-based therapies who meet the above criteria.

Kohne and colleagues also discuss the difficulties in accurate measurement of PS in which the traditional systems of the Eastern Cooperative Oncology Group (ECOG) and Karnofsky PS might be limited in this setting. They suggest that functional reserve and life expectancy should be evaluated best in older patients by a comprehensive geriatric assessment and provide information on that type of measurement. The scale should include information on several factors, especially home environment, social support and comorbidities as well as polypharmacy factors. The article reviews key studies of commonly used chemotherapy drugs and regimens for mCRC and information available on these agents in the elderly.

The authors conclude that more patients are eligible for treatment in the second and third line setting, and elderly patients meeting specific criteria may be good candidates for combination protocols such as FOLFIRI and FOLFOX, although targeted therapies require further evaluation in the elderly. The elderly are represented adequately in clinical trials relative to their diagnoses of cancer; but more studies are needed to examine therapies in this population.³

References

Ries LAG, Harkins D, Krapcho M. et al. Contents of the SEER Cancer Statistics Review, 1975-2003. National Cancer Institute, Bethesda, MD. Retrieved May 1, 2008 from http://seer.cancer.gov/csr/1975_2003/results_merged/sect_06_colon_rectum.pdf
Kohne CH, Folprecht G, Goldberg RM, et al. Chemotherapy in elderly patients with colorectal cancer. Oncologist. 2008;13:390-402.
Lewis JH, Kilfore ML, Goldman DP, et al. Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol. 2003;21:1383-1389.

4-25-08 – Bevacizumab, Capecitabine, and Oxaliplatin: Neoadjuvant Therapy for Potentially Curable Metastatic Colorectal Cancer (mCRC)

Metastasis to the liver is quite common in patients with colorectal cancer, with 25% of the patients presenting with liver disease at diagnosis, and an additional 25% to 45% developing liver metastases if the disease recurs. Although these patients have a poor prognosis, there have been advances in treatment for this population. Selected patients can derive benefit from receiving neoadjuvant chemotherapy and subsequent surgical resection of their disease.

Gruenberger and colleagues sought to determine the effect of bevacizumab, a vascular endothelial growth factor receptor inhibitor (VEGF), currently approved in the first and second line setting for mCRC, when given to patients prior to surgical resection. Since this monoclonal antibody can inhibit wound healing, current recommendations are to wait at least 28 days after surgery prior to initiating therapy with bevacizumab. The purpose of the study was to determine the impact of neoadjuvant treatment with bevacizuamb and chemotherapy.

A total of 56 patients with mCRC liver metastases who were deemed potentially curable by resection were entered on this single-center, nonrandomized phase II trial. The subjects were considered to be at high risk for early recurrence. The risk factors included:

Synchronous liver metastases
Metastatic disease developed within one year after primary resection
Lymph node-positive primary tumors
More than one liver metastasis
Liver metastasis larger than 5cm
Positive CEA level

The protocol called for patients to receive biweekly bevacizumab plus oral capecitabine and oxaliplatin for six cycles, holding the bevacizumab during the sixth cycle of therapy allowing 5 weeks between the VEGF inhibitor treatment and surgery.

The patients showed the following responses to the therapy:

Objective response to neoadjuvant chemotherapy was achieved in 41 patients (73%)
No increased intraoperative bleeding events or wound-healing complications were observed in any patients despite the addition of bevacizumab
Three patients (6%) required blood transfusions
One patient required further surgery
Postoperative liver function and regeneration were normal in all but one patient

The results of the study led the researchers to conclude that bevacizumab can be safely administered to patients with mCRC requiring liver resection in the pre-operative setting, with cessation of therapy at least five weeks prior to surgery without complications of wound healing or increase in severity of bleeding. The results also showed that neoadjuvant bevacizumab does not negatively affect regeneration of liver after surgical resection, despite the known effects of bevacizumab on wound healing.

Reference

Gruenberger B, Tamandl D, Schueller J, et al. Bevacizumab, capecitabine, and oxaliplatin as neoadjuvant therapy for patients with potentially curable metastatic colorectal cancer. J Clin Oncol. 2008;26:1830-1835. Abstract available at: http://jco.ascopubs.org/cgi/content/abstract/26/11/1830

4-9-08 – Another Benefit to FOBT CRC Screening

The United Kingdom (UK) Bowel Cancer Screening Pilot Study involved a population-based sample of 187,777 men and women aged 50-69 years in central England to participate in biennial fecal occult blood test (FOBT) screening for CRC by mail with a home-use FOBT kit. The response rate was 56.8% (81,120), with positive FOBT results in 1.9% (1,541) of respondents.

Drs Goodyear, Leung, Menon, et al, reported on a reduction in emergency presentations and improved 30-day mortality of CRC as a result of FOBT screening in the February issue of Gut. The primary goal of their study was to determine the effects of the Bowel Cancer Screening Pilot on emergency and elective cancer workload; the secondary aims were to assess the effects of FOBT screening on Dukes staging, mortality and stoma formation for patients admitted as an emergency with CRC.

Compared to the baseline pre-screening year (1999), there was a steady decrease in the total number of CRC emergency admissions following the initiation of FOBT screening in the year 2000. In 1999, 60 (29.4%) of 204 patients with CRC were admitted as an emergency. By 2004, the fifth year of screening, only 32 (15.8%) of 202 CRC cases were admitted as an emergency (p=0.001). A significant reduction in the 30-day mortality rate was also observed, from 48% in 1999 to 13% in 2004 (p<0.05).

The authors commented that Dukes stage C carcinomas remained the predominant stage presenting as emergencies throughout the 1999-2004 study period. They suggest that the impact of CRC screening over the 5-year period “is the result of increased detection of asymptomatic malignancies…increased public awareness of the symptoms of CRC, together with a change in attitudes and referral patterns of general practitioners.”

Reference

Goodyear SJ, Leung E, Menon A, et all. The effects of population-based faecal occult blood test screening upon emergency colorectal cancer admissions in Coventry and north Warwickshire. Gut. 2008; 57(2):218-222. Link to abstract http://gut.bmj.com/cgi/content/abstract/57/2/218 Full text available to subscribers or through institutional access.

4-3-08 – Cetuximab Infusion Reactions Increased in Certain Geographical Areas of the US

Cetuximab, an IgG1 anti-EGFR monoclonal antibody (MAb), was approved in 2004 for the treatment of metastatic colorectal cancer (mCRC). As such, the drug can be given as a single-agent therapy as well as combined with irinotecan in this setting. Cetuximab is a chimeric MAb and was noted to cause severe infusion reactions in 3% of the patients studied in clinical trials. Three recent papers report a higher prevalence of reactions in specific geographic areas.

O’Neil et al¹ noted the incidence of severe infusion reactions was actually 22% in the states of Tennessee and North Carolina. Makhoul et al² confirmed a significantly higher reaction rate (19%) in Arkansas as well.

Chung and colleagues³ specifically examined reasons for the higher rate of reactions in the March 13 issue of the New England Journal of Medicine. The researchers examined serum samples from four groups of subjects for IgE antibodies against cetuximab.

76 pretreatment case subjects who had received cetuximab primarily in Tennessee, Arkansas, and North Carolina
72 control subjects in Tennessee
49 control subjects with cancer in Northern California
341 female control subjects in Boston.

The results of the study showed

Of 76 patients treated with cetuximab, 25 had a hypersensitivity reaction to the drug (33%)
In 17 of the subjects, IgE antibodies against cetuximab were found in pretreatment samples (68%)
Patients who did not have a hypersensitivity reaction, only 1 out of 51 had antibodies
(P<0.001)
IgE antibodies against cetuximab were found in

15 of 72 (21%) patients serving as control subjects from Tennessee
3 of 49 (6%) samples from Northern California
2 of 341 (<1%) subjects from Boston

The IgE antibodies are specific for an oligosaccharide, galactose-α-1,3-galactose, which is present on the Fab (fragment antigen binding) portion of the cetuximab heavy chain. In other words, the region of the antibody that recognizes and binds to the antigen.

This research shows that in most of the subjects in the geographic area who have a hypersensitivity reaction to cetuximab, IgE antibodies against the cetuximab MAb were present in the serum of those patients before therapy was given. Cetuximab is produced in the mouse cell line SP2/0, which expresses the gene for a-1,3-galactosyltransferase.³

All humans have IgG antibodies for the oligosaccharide galactose-α-1,3-galactose and natural exposure to this substance seems to produce IgE antibodies against it in specific people.³ This may put these patients at risk for hypersensitivity reactions when they receive MAb therapy. The researchers have discovered a mechanism for the hypersensitivity to cetuximab for some patients but the causative agent is not yet identified, and further research needs to be conducted to further identify patients at risk prior to therapy.

References

O’Neil BH, Allen R., Spigel DR, et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol. 2007;25:3644-3648. Available at Breaking News 9/28/07
Makhoul I., Siegel E, Hutchins A, et al. Cetuximab-related first infusion reaction (FIR) in colorectal cancer (CRC) and other cancer (CA) patients (Pts.). Abstract No: 381. ASCO 2008 Gastrointestinal Cancers Symposium. Retrieved March 19, 2008 available here.
Chung CH, Mirakhur B, Chan E, et al. Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med. 2008;358:1109-1117.

3-28-08 – Colorectal Cancer (CRC) is Preventable, Treatable and Beatable: However Screening Remains Low

CRC is one of the few cancers with an effective method of detecting abnormalities, such as polyps, before cancer ever develops. The American Cancer Society (ACS) recommends that all asymptomatic adults begin colon cancer screening at age 50. Yet the ACS reports that slightly more than 50% of adults older than age 50 have been screened for CRC.¹

Recently the ACS has recommended two additional screening tests to prevent or detect CRC. These additional tests are based on preliminary evidence that the results are promising when compared to the gold standard of colonoscopy. With the addition of the following 2 tests, the current ACS screening options are now seven.

The virtual colonoscopy uses a computed tomography (CT) scan to locate abnormal growths. Unlike the standard colonoscopy, this is a noninvasive test.
The newly-recommended stool DNA (sDNA) exams the stool for abnormal DNA associated with cancer. Although noninvasive, the test requires that an entire bowel movement be collected for laboratory examination.

It is important to note that the National Comprehensive Cancer Network (NCCN) guidelines do not include either of these tests in their screening recommendations.² NCCN identifies the virtual colonoscopy and the sDNA as “evolving and promising diagnostic tools for CRC screening.”

Recommended CRC Screening Procedures

The new ACS guidelines separate the tests into two groups: one detects polyps and cancer, and the other primarily detects cancer.

Tests to detect polyps and cancer

Flexible sigmoidoscopy every 5 years ^*
Standard colonoscopy every 10 years
Double contrast barium enema every 5 years ^*
CT colonography (virtual colonoscopy) every 5 years ^*

Tests to detect cancer

Fecal occult blood test (FOBT)^*
Fecal immunochemical test (FIT) every year^*

FOBT or FIT – the take-home multiple sample method should be used
FOBT or FIT – the digital rectal exam is not adequate for screening

Stool DNA (sDNA), interval uncertain^*

^* Standard colonoscopy should be done if tests are positive. People at moderate or high risk for CRC should talk with their health care provider about a testing schedule.

References

American Cancer Society. Cancers facts and figures 2008. Available at: http://www.cancer.org/docroot/PRO/content/PRO_1_1_Cancer_Statistics_2008_Presentation.asp . Accessed March 20, 2008.
NCCN. Colon Cancer. Treatment guidelines for patients with cancer. v1.2008. Available at: http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf. Accessed March 20, 2008.

3-28-08 – Nonpolypoid (flat and depressed) Colorectal Neoplasms

Colorectal cancer has long been thought to stem from polypoid adenomas, which are generally described as raised, rounded lesions that are well-elevated above the colon mucosa. This makes them relatively easy to detect during routine screening colonoscopy. In contrast, nonpolypoid colorectal neoplasms (NP-CRNs) are only slightly elevated, flat or slightly depressed, making them more difficult to visualize during the procedure.

A study reported by Soetikno et al in the March 5, 2008 issue of the Journal of the American Medical Association (JAMA) found that what was thought to be an unusual presentation of colorectal polyps – nonpolypoid – was relatively common and had a greater association with carcinoma compared with polypoid neoplasms.

The study took place in a Veterans Affairs hospital in California and enrolled 1819 patients undergoing elective colonoscopy. Carmine indigo dye was used to help visualize NP-CRNs. At least 1 superficial colorectal neoplasm was identified in 764 subjects (42% of the study cohort). NP-CRNs were diagnosed in 170 patients (9.35%.) The prevalence of flat and depressed types of NP-CRNs was found in 158 patients (8.58%.)

Previous studies had reported a higher prevalence of NP-CRNs in the Asian population and other studies demonstrated that NP-CRNs are difficult to detect using computed tomography colonography. Soetikno and colleagues found that NP-CRNs are a relatively common finding during colonoscopy among white patients in a single Veterans Affairs population, with a prevalence of 9.3%. The NP-CRN lesions were more likely to contain carcinoma compared with polypoid neoplasms, independent of lesion size.

Reference

Soetikno RM, Kaltenbach T, Rouse RV, et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA. 2008;9: 1027-1035. For those with full-text access to JAMA, an accompanying narrated video demonstrating the use of carmine indigo dye and visualization of NP-CRNs is available at http://jama.ama-assn.org/cgi/content/full/299/9/1027/DC1.

3-17-08 – Cetuximab: Every 2 Week Regimen in Treating Patients With Metastatic Colorectal Cancer (mCRC)

Cetuximab is a chimeric monoclonal antibody (moAb) targeting the epidermal growth factor receptor (EGFR), and was approved for treatment of mCRC in 2004. It is administered weekly (250 mg/m²) after an initial loading dose of 400 mg/m². Tabernero et al¹ discusses cetuximab given as an every 2 week regimen in a review paper in the March issue of The Oncologist. The authors reviewed several studies that investigated the relationship between cetuximab-associated rash and response to treatment at the approved dose or at escalating doses up to a maximum of 500 mg/m² per week.

Since most chemotherapy schedules are every two or three weeks, a less frequent dosing schedule of cetuximab would be advantageous for the patient as well as the health care team. The authors reviewed preliminary results of a two part, phase I study of patients with mCRC who received the loading dose of cetuximab (400 mg/m²), followed by 250 mg/m² per week or doses of 400, 500, 600, and 700 mg/m² every two weeks.² Those results showed that the 500 mg/m² dose every two weeks had

Predictable pharmacokinetics mimicking the approved weekly dosing regimen
Active serum concentrations of the drug throughout the two week dosing period
Efficacy and safety similar to the weekly dosing regimens

The preliminary data suggests that the every two week dosing regimen may be a potential alternative and benefit for some patients to the approved weekly schedule, after the initial loading dose of 400 mg/m². The authors cautioned that the data came from small studies and preliminary results from an ongoing phase I study. Ongoing phase II studies are investigating every 2 week administration of cetuximab with other chemotherapy agents in both first-line and subsequent-lines of therapy for this common cancer.

References

Tabernero J, Pfeiffer P, Cervantes A. Administration of cetuximab every 2 weeks in the treatment of metastatic colorectal cancer: an effective, more convenient alternative to weekly administration? The Oncologist. 2008;13:113-119.
Tabernero J, Cervantes A, Martinelli E, et al. Optimal dose of cetuximab (C) given every 2 weeks (q2w): a phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of weekly (q1w) and q2w schedules in patients (pts) with metastatic colorectal cancer (mCRC). J Clin Oncol. 2006;24;(18 suppl):142s

12-18-07 – Smoking Increases Risk of Rectal Cancer

A pooled analysis by Paskett, et al, of the association between cigarette smoking and colorectal cancer (CRC) among participants in the observational study and the three clinical trials of the Women's Health Initiative (WHI) was published in the November 21, 2007 issue of the Journal of the National Cancer Institute. The study reports that smoking increases the risk of developing rectal cancer. Smoking is known to increase risks of developing several different types of cancer, such as lung, breast, and bladder cancers; however, its effects on colon and rectal cancer are less clear. The WHI included data on smoking habits and rates of colon and rectal cancer from nearly 147,000 individuals. Participants in WHI reported detailed smoking histories upon enrollment and were followed for approximately eight years.

Rates of colon cancer were not increased among smokers.
Second-hand smoke exposure did not increase the risk of colon or rectal cancers.
Rates of rectal cancer were nearly doubled among smokers compared with never-smokers.

Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with CRC in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer in women. The results of this study cannot be generalized to men. Nurses caring for women who are smokers may wish to share this information with their patients and educate them regarding smoking cessation programs and regular screening for rectal cancer.

12-14-07 – Assessing and Treating Early-Stage Colon and Rectal Cancer: Summary of the 2007 Santa Monica Conference

In the November 15, 2007 issue of Clinical Cancer Research, Rosen et al. reported on a summary statement of recommendations from a multidisciplinary meeting of surgical, medical, pathology and radiation oncology experts. The objective of the meeting was to review new information for the assessment and treatment of early-stage colon and rectal cancers and issue recommendations.

Key recommendations included:

Lymph node (LN) status: LN status is the most important prognostic indicator, particularly for stage II disease, despite the fact that many patients do not receive adequate LN dissection. The panel recommended that protocols be adopted to assess <12 LN found on examination.
Staging of rectal tumors: endorectal ultrasonography (EUS) should be considered the gold standard for staging of this disease, and that positron emission tomography (PET) in combination with computerized tomography (CT) is important in detecting recurrent disease and for detection of nodal and distant metastasis.
Future trends in histopathologic staging: histopathologic examination is crucial in defining colorectal cancer, but other approaches, including genotypic and phenotypic studies may also play a role, possibly improving patient prognosis.
Quality of care issues: evaluation of QOL is an essential area, particularly for cancer survivors.
Treatment for locally advanced rectal cancer: neoadjuvant therapy has significant advantages in this group of patients and it has become the standard of care for the treatment of rectal cancer.
Targeted therapy in early-stage colon cancer: treatments look promising in the adjuvant setting, but are not yet standard of care.

The abstract for the above paper is listed below and can be viewed at the following link: http://clincancerres.aacrjournals.org/cgi/content/full/13/22/6853s

A subscription is required for the full text article at Rosen, LS, Bilchik, AJ, Beart RW, et al. New approaches to assessing and treating early-stage colon and rectal cancer: summary statement from 2007 Santa Monica conference. Clin Can Res. 2007;13:6853s-6856s.

12-10-07 – Cetuximab for the Treatment of Colorectal Cancer (CRC)

The New England Journal of Medicine recently reported the indications for treatment with cetuximab for patients with EGFR-expressing CRC. Cetuximab has been shown to reverse drug resistance in patients when administered with irinotecan.¹ Although cetuximab was first approved for treatment of metastatic (mCRC) in 2004, the previous indication was for combination therapy with irinotecan chemotherapy or as solo therapy for those patients who can not tolerate therapy with irinotecan. The new indication is for monotherapy in mCRC after failing both irinotecan- and oxaliplatin-based regimens.

In this report by Jonker et al,² 572 patients with EGFR-expressing mCRC previously treated with a fluoropyrimidine, irinotecan, and oxaliplatin or who had contraindications to treatment with those agents were randomized either to receive an initial dose of 400 mg/m² of cetuximab followed by maintenance weekly infusions of 250 mg/m² plus best supportive care (BSC), or BSC alone. The patients were enrolled between December 2003 through August 2005, The primary end point for this study was overall survival (OS).

When compared to the BSC group patients, the cetuximab group had a significant improvement in OS and in progression free survival (PFS). The study results showed:

Median overall survival of 6.1 months in the cetuximab group versus 4.6 months in the BSC group
Partial responses in 23 of the patients receiving cetuximab versus none in the BSC group
Stable disease in 31.4% of the patients receiving cetuximab versus 10.9% in the BSC group

The patients who received cetuximab also reported better quality of life, with higher physical function and global health status scores (P< 0.05). The patients receiving cetuximab reported rash, although those patients with a rash of grade 2 or higher had a significantly improved survival (P<0.001). The cetuximab patients also reported higher adverse events (78.5% versus 59.1%) than the BSC care group of patients.

This study demonstrates that single agent therapy with cetuximab can improve OS for patients with CRC who have failed other therapies. Although the trial was not blinded (which could account for bias in the assessment of PFS), the authors point out that measurement of OS does not show bias. EGFR is an active target in the therapy of colorectal cancer, although the tyrosine kinase inhibitor EGFR inhibitor agents erlotinib and gefitinib have shown less response in the treatment of this disease, and panitumumab was unable to demonstrate an improvement in OS. This new indication provides an additional treatment option for patients with this common disease.

References

Cunningham D, Humblet Y, Siena S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004; 351:337-345.
Jonker DJ, O’Callaghan CJ, Karapetis CS, et al. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007;357:2040-2048. Available at: http://content.nejm.org/cgi/reprint/357/20/2040.pdf

11-29-07–Report Links Obesity and Cancer

A recent retrospective meta-analysis reports increasing evidence of a link between obesity and the risk of developing certain types of cancer. An international expert panel reviewed more than 7,000 published studies related to diet, exercise, weight and cancer. The report was the work of the American Institute for Cancer Research and the World Cancer Research Fund International. The result of the analysis was announced at a press conference in November 2007, and is available at www.dietandcancerreport.org.

Excess body fat increases the risk of cancer of the colon, kidney, pancreas, esophagus and uterus, as well as postmenopausal breast cancer. The risk of CRC increases by 21% for every 1.7 ounces of processed meat consumed a day. There is a link with the intake of red meat. The report advised limiting red meat to 18 ounces of cooked meat weekly.

Alcohol was linked to various cancers such as those of the mouth, throat, larynx, esophagus, breast, colon and liver. For some populations, such as older women, the risk of breast cancer begins to rise with as much as a single glass of wine daily.

The panelists issued these recommendations for cancer prevention:

Be as lean as possible within the normal range of body weight
Be physically active on a daily basis
Limit consumption of energy –dense foods. Avoid sugary drinks
Eat mostly foods of plant origin
Limit intake of alcoholic drinks
Limit consumption of salt
Strive to meet nutritional needs through diet alone
Limit consumption of red meat
Eliminate processed meats from the diet
Women should breastfeed if possible
Cancer survivors should follow cancer prevention guidelines

One of the goals of the report was to educate people to the fact that cancer may be the result of many long-term influences of the choices we make. Cancer is preventable for the most part. It is estimated that four million deaths worldwide could be prevented annually if individuals improved their diet and increased their activity levels.

It is important to note that this meta-analysis has not been peer-reviewed nor published in a peer-reviewed journal.

10-30-07 – Diets High in Choline May Raise Risk of Colorectal Polyps in Women

According to the results of a study published in the Journal of the National Cancer Institute, high intake of choline may be linked with an increased risk of colorectal polyps (adenomas) in women. Prior studies have suggested that folate, a water-soluble B-vitamin, may reduce the risk of colorectal adenomas by protecting against genetic changes.

Choline is a nutrient that shares some biologic functions with folate, and researchers have hypothesized that choline may also reduce the risk of colorectal adenomas. Major food sources of choline include red meat, eggs, poultry, and dairy products.

Researchers evaluated information from the Nurses’ Health Study, focusing on 39,246 study participants who were initially free of cancer and polyps and who had at least one sigmoidoscopy or colonoscopy between 1984 and 2002. During follow-up, 2,408 of these women were diagnosed with a colorectal adenoma. A self-administered dietary questionnaire was used to assess choline intake.

Compared to women with the lowest intake of choline, women with the highest intake were 45% more likely to develop a colorectal adenoma. The finding that higher choline intake may increase the risk of colorectal polyps was unexpected noting, however, that the apparent link between choline and colorectal adenoma could be due to other components of choline-containing foods rather than to choline intake, and the relationship should be investigated further.

References

Journal of the National Cancer Institute

http://jnci.oxfordjournals.org/cgi/reprint/99/16/1213-a

10-19-07 – Annual Report to the Nation on the Status of Cancer

The 2007 annual report from the nation’s leading cancer organizations (American Cancer Society, National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries) provide an annual update on cancer occurrence and trends in the United States. Findings show cancer death rates decreased on average 2.1 percent per year from 2002 through 2004, nearly twice the annual decrease of 1.1 percent per year from 1993 through 2002.

The findings are in the “Annual Report to the Nation on the Status of Cancer, 1975-2004, Featuring Cancer in American Indians and Alaska Natives” published online October 15, 2007 (www.interscience.wiley.com/cancer/report2007) and appearing in the November 15, 2007, issue of Cancer.

Colorectal cancer incidence rates decreased by more than 2.0 percent per year for men and women, likely due to prevention through the removal of precancerous polyps. Death rates decreased for the majority of the top 15 cancers in men and women. Important declines were noted for the three leading causes of cancer deaths in men: lung, prostate and colorectal cancers. In women, deaths rates from colorectal cancer and breast cancer decreased, while the rate of increase for lung cancer deaths slowed substantially.

References

Espey DK, et al. Annual report to the nation on the status of cancer, 1975-2004, featuring cancer in American Indians and Alaska Natives. Cancer. Published online, October 15, 2007 (DOI: 10.1002/cncr. 23044); print issue date, November 15, 2007.

9-28-07 – Cetuximab-Related Hypersensitivity Reactions: Tennessee and North Carolina

Monoclonal antibodies (mAb) have the potential of causing hypersensitivity (HSR) reactions, although the rate varies for each agent. Both cetuximab (chimeric mAb) and panitumumab (fully-human mAb) are approved in the treatment of metastatic or advanced colorectal cancer. In clinical trials, the incidence of severe HSR was:

Cetuximab – 3%
Panitumumab – 1%

There are antedotal reports of higher incidences of HSR in patients receiving cetuximab residing in the southeastern United States.

These patients had a variety of solid tumor types, including colorectal cancer. Three research units in Tennessee and North Carolina

Analyzed data of 88 patients receiving cetuximab in clinical trials and an additional 55 patients treated outside the clinical trial setting
Report that 22% had grade 3 or 4 HSRs despite receiving the recommended premedication
Found all HSRs occurring during the first dose

The researchers reported a strong relationship between the patient's prior allergy history and chance of HSR, indicating that history is a significant predictor of HSR. A recommendation to screen patients for use of cetuximab based on allergy history could be suggested by the reported data. However, it is interesting to note that patients with a negative allergy history had a rate of grade 3 or 4 HSR, twice as high as previously reported (8%). The authors of the study suggest that continued study of the specific predictors of HSR is needed; and patients receiving this agent in this geographic area should be monitored closely during their first infusion of cetuximab.

Reference: O'Neil, BH, Allen, R, Spigel, DR et al. High incidence of cetuximab-related infusion reactions in Tennessee and North Carolina and the association with atopic history. J Clin Oncol, 2007;24:3644-3648.

9-7-07 – Arterial Thromboembolic Events in Combination Chemotherapy + Bevacizumab: A Meta-analysis

In an August issue of the Journal of the National Cancer Institute, Scappaticci and colleagues reported on the incidence of arterial or venous thromboembolic events during chemotherapy vs. chemotherapy plus bevacizumab in a variety of cancer types and chemotherapy regimens. They concluded that the combination treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with an increased risk of arterial thromboembolism but not venous thromboembolism.

Findings

Pooled safety data were analyzed from 5 randomized, controlled trials (N=1745) of patients with metastatic colorectal, breast, or non–small-cell lung carcinoma. Combined treatment with bevacizumab and chemotherapy, compared with chemotherapy alone, was associated with

Increased risk for arterial thromboembolic event (Hazard ratio [HR] = 2.0, 95% confidence interval [CI] = 1.05 to 3.75; P = .031)^*
No risk for a venous thromboembolic event (HR = 0.89, 95% CI = 0.66 to 1.20; P = .44)^†

The absolute rate of developing an arterial thromboembolism was

5.5 events per 100 person-years for those receiving combination therapy
3.1 events per 100 person-years for those receiving chemotherapy alone (ratio = 1.8, 95% CI = 0.94 to 3.33; P = .076).

Development of an arterial thromboembolic event was associated with a prior arterial thromboembolic event (P<.001) or age of 65 years or older (P = .01). Risk factors for an arterial thromboembolic event included a prior arterial thromboembolic event or age =65 years.

One limitation of the study was associations between risk

Arterial thromboembolic event and different tumor or histologic types
Different chemotherapeutic agents combined with bevacizumab, and
Different disease settings (especially, metastatic vs. adjuvant settings) were not be assessed

Therefore, generalizations as to risk in various disease states or between different chemotherapy/bevacizumab regimens cannot be made on the basis of this study.

A discussion of Venous Thromboembolism can be found here.

Implications for nursing

The risk factors for arterial thromboembolism should be considered when making treatment decisions for individual patients and patients should be educated about the signs or symptoms of arterial thromboembolism when being treated with chemotherapy + bevacizumab. The bevacizumab (Avastin) package insert states Avastin should be permanently discontinued in patients who experience a severe arterial thromboembolism. The safety of resuming bevacizumab therapy has not been studied.

Reference: Scappaticci FA, Skillings JR, Holden SN et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Can Inst. 2007;99:1232-1239. Available full text without charge or subscription at http://jnci.oxfordjournals.org/cgi/reprint/99/16/1232

^*Hazard ratio is a clinical trial statistic that compares 2 treatments. If the hazard ratio is 2.0, the rate of an occurrence in one treatment group (combined treatment) is twice the rate in the other group (chemotherapy alone).

^†Since the hazard ratio was <1, there is little chance of developing a venous thrombosis.

8-20-07 – Low Intake of Fruits and Vegetables May Increase Colorectal Cancer (CRC) Risk Especially for Men

Remember when your mother told you to eat your veggies? Turns out she may have been right, at least for men. A recent study in the American Journal of Epidemiology suggests an increased risk of CRC for men with a low intake of vegetables. Fruits and vegetables have been associated with cancer-fighting components such as vitamin C, carotenoids, folate, fiber, and flavonoids.

Dr. Yikyung Park and others at the National Cancer Institute examined the association between fruit and vegetable intakes and risk of CRC in the National Institute of Health – American Association for Retired Persons (NIH–AARP) Diet and Health Study. They followed 488,043 men and women aged 50–71 years. During a 5-year follow-up, 2,972 incident CRC cases (1%) were identified.

Study results showed that

Men who consumed less than a single serving of vegetables daily (considered very low) had a 26% greater chance of having CRC than men who consumed two or more servings per day.
Men with the highest reported vegetable intake (particularly green-leafy vegetables) had an 18% lower risk of developing CRC when compared with men who ate fewer servings.

The study did not show the same correlations in women. This gender difference may be attributable to reporting errors, since previous studies involving women have shown over reporting of foods perceived as healthy. Fruit intake did not correlate with risk of CRC in either men or women.

Park Y, Subar AF, Kipnis V, et al. Fruit and vegetable intakes and risk of colorectal cancer in the NIH–AARP diet and health study. Am J Epidemiol. 2007;166:170-180.

Subscription required for the full-text article. The abstract is available here: http://aje.oxfordjournals.org/cgi/content/abstract/166/2/170

Further information may be found concerning the NIH-AARP Diet and Health Study online at: http://dietandhealth.cancer.gov/

8-1-07 – Omega-3 Polyunsaturated Fatty Acids May Reduce Colorectal Cancer (CRC) Risk

Research recently published in the American Journal of Epidemiology suggests that a diet rich in omega-3 polyunsaturated fatty acids (PUFAs) may reduce the risk of developing CRC. Omega-3 PUFAs are found in fish, nuts, seeds and oils from plants.

The intake of omega-6 PUFAs, found in some vegetable oils, such as soybean, sunflower, and safflower, has no impact on the risk of CRC. It is suggested this is likely due to the different biologic action of omega-3 and omega-6 PUFAs.

Dr. Evropi Theodoratou and colleagues from the University of Edinburgh, UK stressed the importance of knowing the type of fatty acids involved in the etiology and prevention of CRC.

The national prospective case-controlled study in Scotland included 1,455 incident cases and 1,455 controls. The researchers found that the patients with cancer consumed omega-3 PUFAs in lower amounts than the control subjects who were cancer-free.

Dr. Theodoratou and colleague Dr. Harry Campbell noted that people who consumed the highest level of omega-3 PUFAs had a 37 percent lower risk of CRC when compared to people with the lowest level. Eicosapentaenoic and docosahexaenoic acids*, those present in oily fish, had the strongest association. They noted that more study is needed to support omega-3 PUFAs protective effect against CRC.

People with the highest docosahexaenoic acid intake had 41 percent lower odds of CRC, while those who consumed the highest eicosapentaenoic acids had a 37 percent lower odds, when compared to people with the lowest intake of these PUFAs.

It was noted that people with CRC had diets high in saturated, monosaturated and trans fatty acids, mainly found in meats, but it was not significant to the risk of CRC when the models were adjusted.

* The National Institutes of Health suggests these acids alone or in combination decrease inflammation.

Theodoratou E, McNeill G, Cetnarskyj R, et al. Dietary fatty acids and colorectal cancer: case-control study. Am J Epidemiol. 2007;166:181-195.

Subscription required for the full-text article. The abstract is available here:

7-27-07 – Inverse Relationship Between Plasma Levels of Vitamin D and Colon Cancer

A report published in the July 18, 2007 issue of the Journal of the National Cancer Institute added information to the growing body of literature on the protective effects of vitamin D [25(OH)D] with regard to colorectal cancer (CRC) risk. Wu, et al., conducted a nested case-control study* within the Health Professionals Follow-up Study (HPFS), a large observational study of male health professionals living in the US. Results showed that higher plasma 25(OH)D concentrations were associated with a decreased risk of colon cancer among participants in the HPFS and with decreased risks of colon and colorectal cancer in the pooled analysis. The HPFS findings were also compared to data from the Nurses Health Study (NHS).
* cohort followed over time with both cases and controls in the same cohort.

Between 1993-2002

179 CRC patients were diagnosed in the HPFS cohort
These patients were matched with 356 control subjects by age and month/year of 25(OH)D blood collection
Results were also pooled with previously published results from the Nurses’ Health Study (NHS) cohort

Findings

In the HPFS, a non-statistically significant inverse association between higher plasma 25(OH)D concentration and risk of CRC and a statistically significant inverse association for colon cancer was observed (highest versus lowest quintile: odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.24 to 0.89; P_trend = .005)
After pooling the results from the HPFS and NHS, higher plasma 25(OH)D concentrations were statistically significantly associated with decreased risks of both colorectal cancer (highest versus lowest quintile, OR = 0.66, 95% CI = 0.42 to 1.05; Ptrend = .01) and colon cancer (highest versus lowest quintile, OR = 0.54, 95% CI = 0.34 to 0.86; P_trend = .002)
Opposite relationships between plasma 25(OH)D levels and risk of rectal cancers were found among men (positive) and women (inverse). An unexpected observation was that the inverse association with 25(OH)D concentrations was much stronger for both lean and physically active men and women but much weaker in overweight and inactive individuals
The magnitude and consistency in both cohorts suggest that this observation may not have been due to chance

Limitations to this study include

Small sample size and short follow-up period (8 years in HPFS; 11 years in NHS.)
Plasma 25(OH)D concentrations were determined from blood samples provided at only one time-point.

Wu K, Feskanich D, Fuchs, CS, et al. A nested case-control study of plasma 25-hydroxyvitamin D concentration and risk of colorectal cancer. J Natl Cancer Inst. 2007, 99(14):1120-1129.; doi:10.1093/jnci/djm038. A link to the abstract: http://jnci.oxfordjournals.org/cgi/content/abstract/99/14/1120?etoc

7-18-07 – Repeated Hepatectomy in Recurrent Metastatic Colorectal Cancer (mCRC)

The reported rate of recurrence after resection of hepatic CRC metastases is 50%-70% with 30% of these recurrences confined to the liver.¹ In the June 2007 issue of Archives of Surgery, Drs Ahmad, Chen & Bilchik reported on a retrospective analysis of patients with recurrent metastatic colorectal cancer confined to the liver.

A review of 274 consecutive liver resections identified 64 patients who underwent primary liver resection followed by adjuvant systemic chemotherapy.

None of the patients underwent any liver ablation procedures
Nineteen (19) of 28 patients with liver-confined recurrence underwent repeat hepatectomy
Nine (9) of the 19 patients who underwent repeat hepatectomy received a course of neoadjuvant systemic chemotherapy to downsize the metastases

At median follow-up of 38 months after repeat hepatectomy,

Median and 5-year overall survival (OS) were 48 months and 44%, respectively
Median and 5-year disease-free survival (DFS) were 23 months and 26%, respectively
Median and 5-year OS after primary hepatectomy were significantly higher in the 19 patients who underwent repeat hepatectomy than in the 45 patients who did not undergo the repeat procedure (70 months and 73% vs 43 months and 43%, respectively; P=.03.)

The authors note that their study is unique.

No ablative procedures were used in addition to hepatic resection
No comparison was done of the data with respect to neoadjuvant or adjuvant systemic chemotherapy
No survival benefit conclusion can be made for the use of systemic chemotherapy in this study

The authors conclude that multimodal treatment leads to improved survival after resection of hepatic CRC metastases. The risk and survival benefit of repeat hepatectomy approximate those of primary hepatic resections; therefore, repeat hepatectomy should be the initial consideration in recurrent hepatic mCRC.

Link to abstract available at: http://archsurg.ama-assn.org/cgi/content/short/142/6/526 Full-text article requires subsription. Ahmad A, Chen SL, Bilchik AJ. Role of repeated hepatectomy in the multimodal treatment of hepatic colorectal metastases. Archives of Surgery. 2007;143:526-532.

Reference
1. Muratore A, Polastri R, Bousari H, et al. Repeat hepatectomy for colorectal liver metastases: a worthwhile operation? Journal of Surgical Oncology. 2001;76:127-132.

7-6-07 – Infusing Bevacizumab Safely Over 10 Minutes: One Center’s Experience

Reidy & colleagues reported on shorter infusion times of bevacizumab in the July 1 issue of the Journal of Clinical Oncology. Bevacizumab, an important agent in the treatment of metastatic colorectal cancer, is actively being studied in the adjuvant setting. The researchers wanted to investigate if prolonged infusion time for bevacizumab was still required. The initial trials used a 90- 60- 30 minute infusion administration times.

Using computerized pharmacy records, all patients who received bevacizumab at the Memorial Sloan-Kettering Cancer Center (MSKCC) were identified and evaluated for infusion reactions.

Of 1,077 patients who received 10,606 doses of bevacizumab, the first 202 patients received the standard infusion times with no hypersensitivity (HSR) reactions.
All patients were standardized to receive all doses over 30 minutes. No HSR were experienced.
The administration time was again modified to a rate of 0.5 mg/kg/minute

370 patients received a total of 2,311 doses of bevacizumab at 5 mg/kg over ten minutes
1.6% (six patients) experienced minor clinical events thought to be possibly consistent with HSRs, but of nonserious importance

The researchers concluded that the 90 and 60 minutes infusion times are unnecessary. The institution has adopted the policy of nonresearch infusion of bevacizumab as 0.5 mg/kg/min over 10 minutes. Although not consistent with the administration guidelines from the package insert, this study nevertheless represents an important discovery.

In an accompanying editorial, Margolin and Gordon state, “…this report is laudable.” They state that cost savings to center efficiency, third party payers and improving quality of life is only a piece of a bigger puzzle. How reducing infusion time contributes to finding the best therapy for each patient remains the bigger question.

Reidy, DL, Ki Y, Chung JP, et al. Bevacizumab 5 mg/kg can be infused safely over 10 minutes. J Clin Oncol. 2007;25:2691-2695. The abstract may be viewed at the following link: http://jco.ascopubs.org/cgi/content/abstract/25/19/2691

Margolin, K and M. Gordon. Shortening the infusion time of anticancer drugs: Who will benefit? J. Clin. Oncol. 2007;25:2642-2643. The full-text editorial is available at: http://jco.ascopubs.org/cgi/content/full/25/19/2642

6-18-07 – Folic Acid: Preventing Colorectal Adenomas Questionable

Previous epidemiologic studies have suggested that folic acid may assist in primary prevention of colorectal cancer. In a recent study reported in The Journal of the American Medical Association, Cole and colleagues reported that folic acid has no benefit in secondary prevention of colorectal cancer and may increase the risk of high grade and multiple adenomas. In a double blind, placebo–controlled, multi-site trial over a 10-year period (1994-2004), 1021 adults were enrolled to evaluate the chemopreventive effect of folate in secondary prevention. Eligibility criteria included at least one of the following:

At least one histologically confirmed adenoma within 3 months prior to entry; or
At least one histologically confirmed adenomas removed before recruitment and a lifetime history of 2 or more confirmed adenomas; or
>1cm histologically confirmed adenoma removed within 16 months prior to recruitment

In addition, participants were required to undergo colonoscopy within 3 months of enrollment with removal of all known polyps.

Out of the total number of participants, 516 were randomly assigned in a 1:1 ratio to receive folic acid 1mg/day or placebo. They were also randomized separately to receive aspirin 81 mg or 325 mg per day or placebo. Two follow-up colonoscopies were completed at 30-40 months following baseline colonoscopy, and again at 3 or 5 years at the discretion of the participant’s physician.

Participants (n=987) underwent the first interval follow up surveillance colonscopy at ~3years with the following findings noted:

Among those patients receiving folic acid, 44.1% (n=221), developed at least 1 colorectal adenoma vs 42.4% (n=206) for participants receiving the placebo; unadjusted RR, 1.04, 95% confidence interval (CI) 0.90-1.20; P=0.58
The incidence of at least one advanced lesion was 11.4% among patients receiving folic acid (n=57) and 8.6% in those receiving placebo (unadjusted RR, 1.32; CI, 0.90-1.92; P=0.15)

A total of 607 participants (59.5%) underwent the second interval follow up with results as follows:

Incidence rate of at least 1 adenoma was 41.9% (n=127) for the patients receiving folic acid and 37.2% (n=113) for those receiving placebo (unadjusted RR, 1.13; CI 0.93-1.37; P=0.23)
Additionally, at least one advanced lesion was noted for those receiving folic acid 11.6% (n=35) and 6.9% (n=21) for those receiving placebo (unadjusted RR, 1.67,CI, 1.00-2.80; P=0.05)

Folic acid was associated with a higher incidence of 3 or more adenomas at 9.9% (RR.2.32; P=0.007) in comparison to 4.3% of placebo patients. There was also a higher rate of noncolorectal cancers, primarily prostate cancer among those taking folic acid. The investigators concluded, “The evidence for increased risk of adenomas is equivocal and requires further research.” Dr Cole’s team suggested that this line of investigation should have “high priority in view of the fortification of the U.S. food supply with folate, and some suggestions that folate could conceivably increase the risk of neoplasia outside of the colorectum.”

Reference: Cole BF, et al. Folic Acid for the Prevention of Colorectal Adenomas: A Randomized Clinical Trial. JAMA.2007;297:2351-2359. Available full text, free access at http://jama.ama-assn.org/cgi/reprint/297/21/2351

6-13-07 – Hypersensitivity Reactions: Mechanism, Prevention and Management

Hypersensitivity reactions can occur with any cancer therapy and many of the agents used in the treatment of colorectal cancer. Both oxaliplatin (as a platinum compound) and monoclonal antibodies are known to cause hypersensitivity reactions in some patients. A recent article by Heinz-Josef Lenz, MD, FACP published in The Oncologist 2007;12:601-609 discusses a MEDLINE review of recent studies and reviews on hypersensitivity reactions, with emphasis on those papers providing practical information on managing hypersensitivity reactions. The review found that severe reactions are rare (incidence of < 5%), but patients should receive proper premedication and close monitoring should symptoms of hypersensitivity occur.

The article reviews the immunologic mechanisms by which reactions may occur. These mechanisms include:

Type I hypersensitivity: Characterized by rapid contraction of smooth muscle and dilation of capillaries with resultant urticaria, rash, and bronchospasm mediated by immunoglobulinE (IgE) release of histamines, leukotrienes, and prostaglandins. Carboplatin and oxaliplatin are consistent with Type I hypersensitivity reactions
Anaphylactoid response: Produced by mast cells and basophils, this reaction mimics a Type I hypersensitivity response and may be caused by the taxanes and the substance Cremophor EL, which may be responsible for the histamine release and hypotension involved in hypersensitivity reactions
Monoclonal antibody reactions: Although the mechanism of action for infusion reactions to the monoclonal antibodies is unknown, they do not appear to be true Type I reactions and induced by cytokine release

The article also includes:

Tables of the platinum compounds, taxanes and monoclonal antibodies with useful information on managing these reactions
Tables on the grading of hypersensitivity and acute infusion reactions and possible signs and symptoms of acute infusion reactions
Discussion of the importance of prevention with appropriate pre-medications
An example of a standing order for managing hypersensitivity reactions

The author concludes that rechallenging with any agents should be based on several different factors, and that despite the rarity of severe reactions, mild to moderate reactions occur frequently in cancer therapy.

The entire article may be accessed free of charge at the following link: http://theoncologist.alphamedpress.org/cgi/reprint/12/5/601.

6-8-07 – Epidermal Growth Factor Receptor Inhibitor-Related Toxicities: Seeking Evidence-Based Practice

Cutaneous toxicities are a common side effect of epidermal growth factor receptor inhibitor (EGFRI) agents. Health care professionals struggle over the strategies for managing these toxicities largely due to little information on evidence-based treatments. Lynch & colleagues published in The Oncologist 2007;12:610-621 the results of an international and interdisciplinary EGFRI dermatologic toxicity forum, where experts reviewed the mechanisms of action, toxicities as well as commonly used therapeutic interventions. Their goal was to come to consensus on management strategies.

An outcome of the forum is a three-tiered toxicity grading system (mild, moderate and severe) specific for EGFRI agents. The new grading system, designed as an algorithm, assists clinicians in creating a step-wise approach to therapeutic interventions. Currently the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) is used in clinical trials but is limited to the uniqueness of EGFRI.

The article also includes helpful tables of

Currently approved EGFRI agents as well as those in clinical development
Dermatologic reactions to EGFRI: rash, paronychia, hair changes, dry skin, hypersensitivity reactions and mucositis
Incidence and frequency of EGFRI in pivotal phase 3 trials

The authors conclude that

EGFRI agents are extremely important in the treatment of certain cancers, they have significant dermatologic toxicities for which we currently have limited evidence-based treatment information
More studies are needed to continue the investigation of appropriate treatments for EGFRI agents
The algorithm and toxicity scales

May be used by health care professionals as a tool to discuss the pathology of EGFRI-associated dermatologic toxicities and suggested management strategies
Need to be validated through controlled studies

The full text article is available free of charge at: http://www.theoncologist.com/cgi/reprint/12/5/610

6-1-07 – Two news items reviewing 5 studies on aspirin use and risk of colorectal cancer (CRC)

ASA and Risk of CRC: Role of COX-2 Expression

Regular use of ASA may reduce the risk of CRC that overexpress cyclooxygenase-2 (COX-2). Data on ASA use and the expression of COX-2 in colorectal tumors were examined in two large prospective cohorts of eligible participants (N=130,274). Using biennial questionnaires, enrollees in the Nurses’ Health Study (n=82,911women) and the Health Professional Follow-up Study (n=47,363 men) were followed over 22 years.

Dr Chan and colleagues from the Massachusetts General Hospital and Harvard Medical School report their findings in the May 24 issue of The New England Journal of Medicine 2007;356:2131-2142. Participants who reported regular use of ASA, defined as taking two or more standard (325 mg) ASA tablets per week or using ASA two times per week

Were older
Slightly less physically active
More likely to

Use postmenopausal hormones (among women)
Use multivitamins regularly
Be current or former smokers

Consumed more alcohol
Consumed more folate

Over an average of 2.4 million person-years of follow up, 636 incident cases of CRC among users and non users of ASA were available for determination of COX-2 expression. Of these

423 (67%) had moderate or strong COX 2 expression(COX-2 positive)
213 (33%) had weak or absent COX 2 expression(COX-2 negative)

Additional findings reported

Participants who had regular ASA use (two standard tablets per week or use of aspirin at least two times per week) had a significant reduction in relative risk (.64) of CRC in comparison to those who reported less ASA use
Benefit of ASA use appeared to be confined to those cancers with COX-2 expression
ASA use did not appear to be associated with the risk of CRC with weak or absent COX-2 expression
A statistically significant reduction in the number of cases of COX-2 positive cancer was not evident until ASA was used for more than 10 years (multivariant relative risk .59)
There was no statistically significant reduction in the number of COX-2 negative cancers with increase duration of ASA use

A related editorial by Dr Sanford Markowitz from Case Western Reserve suggests that Dr. Chan’s findings support a “powerful role of COX-2 as a key mediator in the development of colon cancer.” These findings “pose important questions about the biological basis and clinical implications of discovering differences between colon cancers that express high and low levels of COX-2.”

Subscription for the full-text is required. The abstract is available at: http://content.nejm.org/cgi/content/short/356/21/2131

6-1-07 – Regular Use of Aspirin May Reduce the Risk Colorectal Cancer

Regular use of aspirin taken long term may reduce the risk of colorectal cancer. The British Doctors Aspirin Trial (n= 5139) and the UK Transient Ischaemic Attack Aspirin Trial (n=937) studied data for a median follow-up of 23 years. Both controlled studies had a treatment period of at least five years with daily aspirin doses of 300mg or higher.

Dr. Peter Rothwell and colleagues reported their finding in the May 12 issue of The Lancet. Patients who took aspirin 300 mg or higher daily for

5 years were 37% less likely to develop CRC
10-14 years were 74% less likely to develop the disease assuming that it takes 10 years for precancerous adenomas to develop

Dr. Rothwell and colleagues also reviewed 19 case controlled and 11 cohort studies (N>1 million). These findings were similar to the two British clinical studies. They recommend that long-term randomized trials are needed before aspirin could be recommended as prophylaxis for CRC.

Access to the abstract and article require a subscription. A summary of the article can be found here: http://www.medpagetoday.com/tbprint.cfm?tbid=5626&topicid=16

In an accompanying editorial, Dr Andrew Chan from Massachusetts General Hospital cautions that due to the risk of bleeding these results are “not sufficient to warrant a recommendation for the general population to use aspirin for cancer prevention.”

Dr. Eric J. Jacobs and colleagues from the American Cancer Society reported the results of the Cancer Prevention Study II Nutrition Cohort (n= 145,000) in the April 18 issue of the Journal of the National Cancer Institute. They found that the long-term use of adult-strength aspirin reduced the risk of colorectal cancer by 32%. The abstract is available here: http://jnci.oxfordjournals.org/cgi/content/abstract/99/8/608

In an accompanying editorial, Drs. Maria Elena Martinez and E. Robert Greenberg from the Arizona Cancer Center, cautioned against using adult dose aspirin in place of regular colon screenings and noted the findings need to be verified to prove a real benefit. Full-text free article is available here: http://jnci.oxfordjournals.org/cgi/content/full/99/8/582

At the 2007 Annual Meeting of the American Association for Cancer Research (AACR), Dr. Aditya Bardia and colleagues from the Mayo Clinic followed 22,507 women who participated in the Iowa Women’s Health Study. They found that women who regularly used aspirin had a 16% reduction in the risk of developing cancer a decade later. They also found no impact on cancer incidence among women who used non-aspirin NSAIDs

This does not mean women should begin to use aspirin regularly, Dr. Bardia states. “However, it does provide provocative evidence that regular aspirin use may play a role in preventing the most common chronic diseases in western countries, namely cancer and heart disease.” Patients should speak with their physicians about the risks and benefits of regular aspirin use before starting a daily dose of adult-strength aspirin.

5-24-07 – Dietary Fiber Intake and Colorectal Cancer (CRC) Risk

Intake of dietary fiber and its protection against CRC has been studied many times with inconclusive results. Two recent studies have examined this question in 2 different populations.

The National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study analyzed a cohort of 291,988 men and 197,623 women aged 50–71 years from 1995-1996. The Japan Collaborative Cohort Study (JACC) studied 16,636 men and 26,479 women aged 40 to 79 years from 1988 to 1990.

The NIH-AARP Diet and Health Study was a large (490,000 men and women) prospective cohort study reported by Dr. Arthur Schatzkin and colleagues in the May 2007 issue of the American Journal of Clinical Nutrition. Diet was assessed using a self-administered food-frequency questionnaire. Over a 5 year period, 2,974 incident cases (.06%) of CRC were identified. Estimating the relative risks (RR) and 95% confidence intervals (CIs), the findings showed that:

Total dietary intake was not associated with a risk for CRC
Fiber from whole-grains showed a modest risk reduction of CRC and stronger reduction for rectal than colon cancer

Full-text of the article requires a subscription. The abstract is available at: http://www.ajcn.org/cgi/content/abstract/85/5/1353

Dr. Kenji Wakai and researchers report the findings of the JACC Study in the April 1, 2007 issue of Cancer Epidemiology Biomarkers and Prevention. They examined a population known for low fiber intake and high incidence of CRC. The results of self-administered food-frequency questionnaires from 43,115 men and women were examined. The mean follow-up of 7.6 years reported 443 cases (1%) of CRC. The researchers report a decreased risk of CRC associated with an increase in total dietary fiber intake. This trend was:

Specific for colon cancer
Larger for men than women
No difference in the risk with water-soluble versus insoluble dietary fiber

The researchers conclude that the role of dietary fiber in preventing CRC remains inconsistent. The need for further study in various populations is suggested.

Full-text of the article requires a subscription. The abstract is available at: http://cebp.aacrjournals.org/cgi/content/abstract/16/4/668

5-11-07 – Risk of Colorectal Cancer (CRC) in Certain Patients With Inflammatory Bowel Disease (IBD)

Chronic inflammation has long been suspected as a risk factor for dysplasia and cancer. Dr. Tine Jess and colleagues at the Mayo Clinic, Rochester MN reported on a case-control study of 43 patients with IBD who were matched 1:3 with controls (n=102). Using conditional logistic regression analysis, the investigators found an increased risk in the odds of developing CRC among the IBD group. The findings of this study confirm emerging data supporting the correlation between chronic inflammation and dysplasia.

Subgroups of IBD patients, those with primary sclerosing cholangitis, severe long-standing IBD, exposure to x-rays (by number of small-bowel x-rays), were at greater risk of developing CRC. Close physician follow-up, colonoscopy, and IBD treatment with 5-aminosalicylates (5-ASA), a class of drugs used to treat IBD, showed questionable protective effects. The study, reported in the April issue of the American Journal of Gastroenterology, is available here

5-11-07 – Magnesium Wasting and EGFR-Targeted Therapy in Patients With Metastatic Colorectal Cancer (mCRC)

In a study at University Hospital Gasthuisberg, Leuven, Belgium, use of epidermal growth factor receptor (EGFR) targeted therapy was associated with magnesium wasting in 95 of 98 patients being treated for metastatic CRC.

Sabine Tejpar, MD, PhD and colleagues reported in Lancet Oncology 2007;8:387-394 that 97% of patients treated with EGFR-targeted therapy had a progressive decrease in serum magnesium concentration. These findings were seen in patients with or without concurrent chemotherapy.

Serum magnesium levels were reviewed at baseline and then every two weeks. Twenty-four hour urine collections were not part of the original design; however baseline values were obtained for 15 patients and 35 patients provided 24-hour urine specimens during treatment.

The findings of this study are

Rate of magnesium loss and duration of treatment determine the onset of hypomagnesemia during treatment with EGFR-targeted therapy. The authors suggest the incidence of magnesium wasting is underestimated because the focus is on patients with low magnesium levels alone, and not also connected with the duration of treatment.
Increasing age was associated with more severe magnesium wasting
Careful monitoring of magnesium levels is important as the symptoms can be subclinical.

Patients with advanced cancer may experience subclinical hypomagnesemia irrespective of concurrent cancer therapy.
Subclinical cardiac abnormalities can be present in grade 2 or worse hypomagnesemia; therefore, caution is urged when prescribing medications that prolong the QT interval

Patients receiving concomitant cisplatin had an increased potential of magnesium wasting
Weekly regimen of IV magnesium did not correct the serum levels; daily treatment was effective in the acute setting
Magnesium levels recover rapidly following discontinuation of EGFR-targeted therapy, suggesting no cellular damage

In an accompanying editorial, Marwan Fakih, MD of the Roswell Park Cancer Institute in Buffalo NY noted that Roswell Park has implemented a cetuximab stop-and-go approach for patients with =grade 3 hypomagnesemia requiring >3-times weekly IV magnesium replacement.

The abstract of this article is available at http://www.thelancet.com/journals/lanonc

4-17-07 – Preventive Health Exams May Provide Opportunities for Cancer Screening

Health plan members who receive preventive health examinations, as opposed to going to a physician only when they are sick, appear more likely to undergo testing for colorectal, breast and prostate cancers, according to a report in the March 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Overview

Preventive or periodic health examinations are not a new concept. Besides a physical examination and medical history, screening, counseling or immunizations may be included.

Dr. Joshua J. Fenton, University of California, Davis, Sacramento, and colleagues assessed the association between preventive health examinations and screening for colorectal, breast or prostate cancer in 64,288 enrollees of a Washington State health plan in 2002 to 2003. Enrollees included:

39,475 patients eligible for colorectal cancer screening
31,379 women eligible for breast cancer screening
28,483 men eligible for prostate cancer screening
Patients were between the ages of 52 and 78

All visited their primary care physician at least once during the study period
More than half (52.4%) received a preventive health examination

Findings

Controlling for other factors influencing cancer screening rates:

Eligible patients who received preventive health examinations were significantly more likely than those who did not receive them to undergo testing for

Colorectal cancer (57.2% vs 17.2%)
Breast cancer screening mammography (74.1% vs 55.9%)
Prostate cancer PSA testing (58.8% vs 21.1%)

The authors’ state, “The associations were particularly strong for colorectal and prostate cancer, for which the health plan provides no centralized screening program,” as it does for mammography.”

Conclusion

They conclude, “In similar populations, the preventive health examination may serve as a clinically important forum for the promotion of evidence-based colorectal, breast and prostate cancer screening, which is not universally recommended.”

The full-text article (subscription required) is available at: Fenton JJ, Cai Y, Weiss NS, et al. How important is the preventive health examination? Arch Intern Med. 2007;167:580-585.

4-4-07 – Vitamin D, Calcium and Oral Contraceptives May Offer Protection Against Colorectal Cancer

Two studies are reported in the April 1 issue of the American Journal of Epidemiology showing reduced risks for colorectal cancer (CRC).

The first study examined the link between calcium and vitamin D intake and risk of CRC in 191,000 subjects (85,903 men and 105,108 women) between the ages of 45 and 75 years who completed a quantitative dietary questionnaire between 1993 and 1996. Over an average of 7 year follow-up, 2110 new cases of CRC were identified (1138 in men and 972 in women).

The second study involved 40,000 women from the Women’s Health Study on ever use of oral contraceptives (OC). Over an 11 year follow-up 267 incident cases of CRC were documented.

In the first study, Multiethnic Cohort Study (Hawaii and Los Angeles)

High total calcium intake (food and supplements) was inversely associated with the risk of CRC in both men and women. The risk reduction was 30% for men and 36 % for women comparing high and low calcium intakes
High intake of dairy products, especially in people who did not take calcium supplements, showed the risk reduction of 23% for men and 34% for women
Total vitamin D intake show an inverse relationship between the CRC risk in men but not women

Dr Song-Yi Park and colleagues from the University of Hawaii conclude that “the findings support the hypothesis of protective roles of calcium, vitamin D and dairy products in the risk of CRC.”

Dr Jennifer Lin and colleagues from the Harvard Medical School hypothesized that exogenous hormone (OC) may provide protection against CRC. The relative risk of women using OC from 6 months to 3 years was 0.61. The decreased risk was minimal with longer use. They also studied reproductive factors such as parity, age of first birth, menarche and menopause.

They concluded no significant association between endogenous hormone and reproductive factors and risk for CRC. They suggest the findings show some “support for a potential role of OC’s in reducing risk for CRC.”

Abstracts for both articles are available at:"http://aje.oxfordjournals.org/content/vol165/issue7/"

3-28-07 – Number of Lymph Nodes Removed Linked to Better Outcome for Patients With Colon Cancer

In colon cancer surgery, the more lymph nodes excised and examined the better the outcome reports George Chang, MD in the March 21 Journal of the National Cancer Institute.

The number of lymph node recovered and examined is supported by many professional societies as an indicator of quality cancer care. Increasing the number from the current recommendation (12) is open to controversy.

Dr. Chang and colleagues from M.D. Anderson Cancer Center in Houston reviewed studies in major medical databases from 1990 to June 30, 2006. They found 17 studies from nine countries totaling 61,371 patients. Sixteen of the 17 studies showed that improved survival was associated with the number of lymph nodes examined for patients with stage II colon cancer. Four of 6 studies included stage III colon cancer with similar results.

The studies differed in their methodology and lymph nodes sampled from a low of 6 to a high of 40. Two studies (US and Italy) were identified as showing significant overall survival when more lymph nodes were examined (20).

The authors point out that the studies were observational and differed in methodology and number of lymph nodes examined. However, they were able to determine survival benefits from examining more lymph nodes than too few. They caution that the strength of this association needs more study because of other quality indicators.

3-23-07 – Simultaneous Resections and Synchronous Liver Metastases: Short and Long Term Surgical Outcomes for CRC

Simultaneous resection of a colorectal lesion and a small liver metastasis is safe. When the liver lesion is more extensive, separate procedures may be the better course. Chemotherapy after hepatectomy, but not before, was also associated with longer survival. Findings were based on a 20-year retrospective study (N=610) comparing post-operative and long-term outcomes after simultaneous and staged colorectal and hepatic resections from 1985-2006 at three centers. These findings were reported by Srinevas Reddy, MD and colleagues at Duke University Medical Center and presented at the 2007 Society of Surgical Oncology Annual Meeting, Washington, DC, Abstract 48.

Patients with simultaneous procedures had

Fewer metastases
Smaller metastatic lesion size, and
Were less likely to have undergone pre-hepatectomy chemotherapy, or
Have major hepatectomies than patients with major hepatic resections

Mortality was similar between the two groups when the hepatectomy was minor. There were significantly more deaths in the simultaneous surgery group requiring a major liver resection.

Recommendations of the study investigators included the observation that newly diagnosed CRC patients might benefit from evaluation at a multidisciplinary center that includes medical and surgical oncologists skilled in colorectal surgery as well as surgeons capable of performing hepatic resections, according to Bryan Clary, MD, a surgical oncologist at Duke University.

3-13-07 - Elderly May Be Under Treated in Refractory Metastatic Colorectal Cancer

The use of oxaliplatin (O) and irinotecan (I) alone or in combination with 5-FU have been studied in randomized clinical trials. However, clinical studies are lacking in the use of O and I in the general population following treatment with 5-FU. Australian researchers report that survival is greater in patients less than 70 years of age.

Dr. Niall C. Tebbutt and colleagues, using 2002 and 2003 Health Insurance Commission (HIC) data of nearly 3000 patients, report their findings in the February issue of the British Journal of Cancer. 75% of patients were younger than 70 years of age; 23% older than 70 and 2% older than 80.

They noted that

2002 data showed 48% of patients received (O) as their initial treatment, rather than (I)
2003 data show an increase to 66% receiving (O) as their initial treatment
Overall, 40% to 45% received both drugs
Survival of 5-FU refractory patients who received either (O) or (I)

67% at 12 months
42% at 6 months
Findings are lower than reported in clinical trials: 80% at 6 months and 50% at 1 year
Largest difference in survival was between patients who received both drugs versus those who receive treatment with one agent
Results show that overall survival was similar in both age groups: 25% for those <70 years of age and 22% for those >70

In conclusion, the researchers note “We found higher survival of younger patients irrespective of the type of initial treatment, perhaps because clinicians treat older patients less intensively.”

3-06-07 – Radiation for Rectal Cancer May Protect for Prostate Cancer

Radiation for rectal cancer may reduce the risk of prostate cancer development according to an abstract presented at the ASCO 2007 Prostate Cancer Symposium. Dr Karen Hoffman, clinical fellow in radiation oncology at Massachusetts General Hospital in Boston MA stated that analysis of SEER data indicated the risk of prostate cancer in men who received external beam RT for rectal cancer was about 70% lower than would be expected in the general population. The average age of the men at the time of treatment was 71 years. Further information and a copy of the abstract is available on the ASCO website is available here

2-13-07 – Benefit of Vitamin D in Cutting Risk of CRC: A Meta-analysis

A meta-analysis of published data indicates that a daily intake of 1000 to 2000 IU (25 to 50 micrograms) vitamin D₃ may safely reduce the incidence of CRC.

The Women’s Health Initiative showed that a low dose of vitamin D over a period of 7 years did not lower the incidence of CRC. A meta-analysis, identified using PubMed, reveal that safe use of higher doses of Vitamin D may lower the risk of CRC.

The circulating metabolite of vitamin D is 25-hydroxyvitamin D (25(OH)D). The normal range can be seasonal based on available sunlight. A severely low level is 12 ng/mL (30 nmol/L) to a desirable level of 25-30 ng/mL (63 to 75 nmol/L).

Dr. Edward D. Gorham reports in the March issue of the American Journal of Preventive Medicine, that the five studies in the meta-analysis showed an association between the rise in serum levels of 25(OH)D and a decreased risk of CRC.

In the final pooled analysis, the serum 25(OH)D level of =33 ng/mL (83 nmols/L) is associated with a 50% decrease risk of CRC relative to a level of =12 ng/mL (30 nmols/L).

The researchers from the Naval Health Research Center in San Diego, California conclude that a daily intake of 1000 to 2000 IU of vitamin D₃ to maintain the serum levels at =33 ng/mL (83 nmols/L) would “substantially” lower the risk of CRC, with minimal risks. They emphasize that the National Academy of Sciences recommend that a daily dose of 2000 IU vitamin D₃ is safe.

1-31-07 – Resource: New Text

The Oncology Nursing Society has released a new text Gastrointestinal Cancers with Joyce P. Griffin-Sobel, as the editor. Chapters in this new volume include: an overview of GI cancers; anatomy and physiology of the GI tract, biology; prevention and screening; esophageal and gastric cancers; colorectal and anal cancers; nursing care of patients with GI cancers, symptom management and evidence-based practice. Information is available at: http://esource.ons.org/ProductDetails.aspx?sku=INPU0566

1-17-2007 – Incidence and Death Rates Decline for CRC

The American Cancer Society has released 2007 figures as part of their annual statistical report on cancer incidence and mortality. The good news is that cancer-related mortality has decreased for the second consecutive year. "This second consecutive drop in the number of actual cancer deaths, much steeper than the first, shows last year's historic drop was no fluke," says John R. Seffrin, PhD, chief executive officer of the American Cancer Society. "The hard work towards preventing cancer, catching it early, and making treatment more effective is paying dramatic, lifesaving dividends." Both incidence and death rates have dropped for colorectal cancer in recent years. Approximately 112,340 new cases of CRC and 52,180 deaths from CRC are expected in 2007. The full report is available in the Jan-Feb issue of CA: A Cancer Journal for Clinicians, available on the ACS website. A link to a synopsis of the report is available at http://www.cancer.org/docroot/NWS/content/NWS_1_1x_Cancer_Deaths_Down_Again.asp

1-09-2007 – Phase II trial Chemoradiation with Oxaliplatin for Rectal Cancer

The result of a multicenter phase II study of preoperative radiotherapy (RT) and concurrent capecitabine and oxaliplatin (XELOX) plus 4 cycles of adjuvant XELOX in patients with rectal cancer was reported by Rodel et al in the January 1 issue of the Journal of Clinical Oncology (2007;25:110-117). A total of 104 patients were evaluated after receiving preoperative RT with concurrent capecitabine plus oxaliplatin.

Pathologic complete response (pCR) and feasibility of postoperative XELOX were the primary study end points. pCR was achieved in 17 patients; 53 patients showed more than 50% regression of the tumor mass. Four cycles of adjuvant XELOX were administered to 96% of patients, with sensory neuropathy (18%) and diarrhea (12%) being the primary grade 3/4 toxicities.

The authors concluded that preoperative XELOX-RT plus 4 cycles of adjuvant XELOX is an active and feasible treatment for rectal cancer. A phase III study comparing standard FU/LV with XELOX-based multimodality treatment is planned. An abstract with a link to the full-text article can be found at http://www.jco.org/cgi/content/abstract/25/1/110

1-08-2007 – Phase III Trial of XELOX Versus FU/LV: Safety Analysis

The result of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil plus leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer was published in the January 1 issue of the Journal of Clinical Oncology (2007;25:102-109). Schmoll et al reported that 1,864 patients, randomized to receive either XELOX or FU/LV, were included in the safety analysis.

The FU/LV group included both the Mayo and Roswell Park (RP) regimens. Treatment-related adverse events (AEs) in the 2 treatment arms were similar. Patients in the XELOX group experienced less diarrhea and alopecia than did the FU/LV group. XELOX patients experienced more neurosensory toxicity, vomiting, and hand-foot syndrome than did FU/LV patients.

The XELOX group had less grade 3/4 hematologic toxicity but more grade 3/4 gastrointestinal AEs compared with Mayo regimen subset. Compared with the RP subset, the XELOX group had fewer grade 3/4 gastrointestinal AEs and more grade 3/4 hematologic AEs. Grade 3/4 neurosensory AEs and grade 3 hand-foot syndrome were higher in the XELOX group than in both the Mayo and RP subsets.

Efficacy data were not reported at this time but will be reported within the next 24 months. An abstract with a link to the full text is available at http://www.jco.org/cgi/content/abstract/25/1/102.

1-05-2007 – CRC Risk and Statin Use

Reduction of the risk of CRC has been reported to be as high as 50% among statin users.¹ Googan, et al reported the results of a population-based case-control study of 1,809 patients and 1,809 controls with respect to statin type, dose, and duration of use in the January 3 issue of the Journal of the National Cancer Institute (2007;99:32-40).

Regular use of statins for at least 3 months was not associated with a reduced risk of CRC. There was no consistent trend across dose or duration of use. The risk of stage IV cancer was, however, statistically significantly lower among statin users than among nonusers. There was no evidence of an interaction between statin use and nonsteroidal anti-inflammatory drug use.

The authors concluded that the use of statins did not appear to be associated with reduced risk of CRC. The reduced risk of stage IV cancer observed among statin users requires confirmation. The abstract and link to the full-text article are available at http://jnci.oxfordjournals.org/cgi/content/abstract/99/1/32?etoc.

References

Poynter JN, Gruber SB, Higgins PD, et al. Statins and the risk of colorectal cancer.
N Engl J Med. 2005;352:2184-2192

12-27-2006 – Colonoscopy Screening and Early Detection Linked To Medicare Coverage

Insurance coverage is one barrier to screening for colon cancer. The Balanced Budget Act of 1997 required Medicare reimbursement for fecal occult blood testing, barium enema, or sigmoidoscopy, beginning January 1, 1998. Individuals deemed to be at risk for CRC were covered for a colonoscopy.

Dr Cary Gross and colleagues at Yale University School of Medicine examined Medicare data from 1991 to 2003 on the use of colonoscopy in colon cancer patients aged 67 or older. Before coverage, from 1993 to 1997 the rate was 285 procedures per quarter for 100,000 beneficiaries. With coverage, from 1998 to June 2001 the rate increased to 889 per 100,000. With extended coverage, colonoscopy use rose to 1,919 per 100,000.

The researchers report their findings in the December 20 issue of the Journal of the American Medical Association (click here for the abstract) The increase in early-stage diagnosis was significant for proximal lesions during 3 time intervals: 18.1% for 1993 to 1997, 22.2% for 1998 to 2001, and 24.2% for mid 1998 to 2001. Distal lesions were identified more frequently during 1998 to 2001, with no significant increase following that time period.

Although the findings suggest that Medicare funding of colonoscopies may have contributed to increased early diagnosis Dr Gross et al remind us that in the majority of patients, colon cancer is diagnosed at late stages. They warn that economics, upper age limits, and life expectancy need to be considered in view of these findings.

12-27-2006 – Effective Colonoscopy: Link With Time and Tube Withdrawal

Speed in conducting a colonoscopy may not be a measure of effectiveness, according to an Illinois gastroenterology group. Over a 15-month period, 12 board-certified gastroenterologists in private practice studied 7,882 patients to assess their skill in finding adenomas. Some endoscopists were 10 times more effective than others in finding adenomas. Those who took more time with the procedure found more polyps—especially when they withdrew the colonoscope, which is “considered the critical phase at which to assess for neoplasia.”

The study, reported in the December 14, 2006, issue of the New England Journal of Medicine (click here for full-text article ), found that doctors who spent 6 minutes (recommended guideline) or more finding polyps constituted the group that was 10 times more effective. The group now spends at least 8 minutes (using a timer) on withdrawal and has thereby increased detection of adenomas by 50%.

12-4-2006 – Meta-analysis: Evidence That Red and Processed Meats Linked
to CRC Risk

A meta-analysis of prospective studies published through March 2006 show that red and processed meats are positively linked to a risk of CRC. Drs Susanna C. Larrson and Alicja Wolk, of the Karolinska

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General News

7-31-08 – CRC Screening Rates Remain Low in Europe, Australia and the US

7-18-08 – Asians Are Less Likely To Undergo CRC Screening

Reference

References

Reference

References

Reference

4-9-08 – Another Benefit to FOBT CRC Screening

Reference

References

3-28-08 – Colorectal Cancer (CRC) is Preventable, Treatable and Beatable: However Screening Remains Low

Recommended CRC Screening Procedures

Tests to detect polyps and cancer

Tests to detect cancer

References

3-28-08 – Nonpolypoid (flat and depressed) Colorectal Neoplasms

Reference

3-17-08 – Cetuximab: Every 2 Week Regimen in Treating Patients With Metastatic Colorectal Cancer (mCRC)

References

12-18-07 – Smoking Increases Risk of Rectal Cancer

12-14-07 – Assessing and Treating Early-Stage Colon and Rectal Cancer: Summary of the 2007 Santa Monica Conference

12-10-07 – Cetuximab for the Treatment of Colorectal Cancer (CRC)

References

11-29-07–Report Links Obesity and Cancer

10-30-07 – Diets High in Choline May Raise Risk of Colorectal Polyps in Women

References

10-19-07 – Annual Report to the Nation on the Status of Cancer

References

9-28-07 – Cetuximab-Related Hypersensitivity Reactions: Tennessee and North Carolina

9-7-07 – Arterial Thromboembolic Events in Combination Chemotherapy + Bevacizumab: A Meta-analysis

8-20-07 – Low Intake of Fruits and Vegetables May Increase Colorectal Cancer (CRC) Risk Especially for Men

8-1-07 – Omega-3 Polyunsaturated Fatty Acids May Reduce Colorectal Cancer (CRC) Risk

7-27-07 – Inverse Relationship Between Plasma Levels of Vitamin D and Colon Cancer

7-18-07 – Repeated Hepatectomy in Recurrent Metastatic Colorectal Cancer (mCRC)

7-6-07 – Infusing Bevacizumab Safely Over 10 Minutes: One Center’s Experience

6-18-07 – Folic Acid: Preventing Colorectal Adenomas Questionable

6-13-07 – Hypersensitivity Reactions: Mechanism, Prevention and Management

6-8-07 – Epidermal Growth Factor Receptor Inhibitor-Related Toxicities: Seeking Evidence-Based Practice

6-1-07 – Two news items reviewing 5 studies on aspirin use and risk of colorectal cancer (CRC)

ASA and Risk of CRC: Role of COX-2 Expression

6-1-07 – Regular Use of Aspirin May Reduce the Risk Colorectal Cancer

5-24-07 – Dietary Fiber Intake and Colorectal Cancer (CRC) Risk

5-11-07 – Risk of Colorectal Cancer (CRC) in Certain Patients With Inflammatory Bowel Disease (IBD)

5-11-07 – Magnesium Wasting and EGFR-Targeted Therapy in Patients With Metastatic Colorectal Cancer (mCRC)

4-17-07 – Preventive Health Exams May Provide Opportunities for Cancer Screening

Overview

Findings

Conclusion

4-4-07 – Vitamin D, Calcium and Oral Contraceptives May Offer Protection Against Colorectal Cancer

3-28-07 – Number of Lymph Nodes Removed Linked to Better Outcome for Patients With Colon Cancer

3-23-07 – Simultaneous Resections and Synchronous Liver Metastases: Short and Long Term Surgical Outcomes for CRC

3-13-07 - Elderly May Be Under Treated in Refractory Metastatic Colorectal Cancer

3-06-07 – Radiation for Rectal Cancer May Protect for Prostate Cancer

2-13-07 – Benefit of Vitamin D in Cutting Risk of CRC: A Meta-analysis

1-31-07 – Resource: New Text

1-17-2007 – Incidence and Death Rates Decline for CRC

1-09-2007 – Phase II trial Chemoradiation with Oxaliplatin for Rectal Cancer

1-08-2007 – Phase III Trial of XELOX Versus FU/LV: Safety Analysis

1-05-2007 – CRC Risk and Statin Use

References

12-27-2006 – Colonoscopy Screening and Early Detection Linked To Medicare Coverage

12-27-2006 – Effective Colonoscopy: Link With Time and Tube Withdrawal

12-4-2006 – Meta-analysis: Evidence That Red and Processed Meats Linked to CRC Risk

12-4-2006 – Meta-analysis: Evidence That Red and Processed Meats Linked
to CRC Risk