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Thank you for submitting your question to the Expert Panel of ManageCRC.com. For the first time, a question has left our Panel without clear evidence to support a particular practice that has generally been the standard in nearly all the CRC studies investigating 5-FU (e.g. deGramont, A et al. [1997]. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin plus continuous infusion for advanced colorectal cancer: A French intergroup study. Journal of Clinical Oncology 15:808-815) We are assuming you are referring to the deGramont or LV5FU2 regimen. Subscription required for full article. Abstract is free at this link: http://jco.ascopubs.org/cgi/content/abstract/15/2/808 We had thought it might be an issue of 5-FU pharmacokinetics. Although we found several papers discussing the pharmacokinetics of infusional 5-FU vs oral 5-FU, nothing was found suggesting that 5-FU pharmacokinetics in the LV5FU2 regimen was the reason for starting the continuous infusion within 1 hour of completing the bolus administration. Another thought was pharmacokinetics of the 2-hour leucovorin infusion that is given prior to the 5-FU bolus, that is, starting the 5-FU continuous infusion while leucovorin is still active. We will continue to research your question and will advise you if outside sources can lend a hand with this issue. Stay tuned!

Thank you for submitting your question about oxaliplatin extravasation to the Panel of ManageCRC.com. Sometimes it's difficult to tell if an extravasation or infiltration has occurred during the actual infusion. If the patient doesn't report pain or there is no immediate swelling or skin change, both the nurse and patient assume no infiltration of the tissues occurred, although an extravasation may have happened nonetheless. Another possibility in the situation you describe is that a superficial thrombophlebitis has occurred - an irritation of the vein following administration of any IV substance. Superficial thrombophlebitis is generally treated with warm compresses, non-steroidal anti-inflammatory drugs (NSAIDs) and monitoring for signs of infection. For management of a possible oxaliplatin extravasation, we direct you to the ManageCRC.com webpage on extravasation of oxaliplatin at http://www.managecrc.com/html/side-effect-extravasation.asp. There have been recent articles in Oncology Nursing Society (ONS) publications covering many aspects of extravasation. ONS membership is required for access. Go to www.ons.org and click on publications.

Thank you for submitting your question to the Panel of ManageCRC.com. More than 50% of patients undergoing cisplatin chemotherapy experience nausea and vomiting, despite receiving standard antiemetic therapy with serotonin receptor antagonist and corticosteroid combinations. An article published by Schmoll, et al. (Annals of Oncology. 2006; 17:1000-1006) compared an aprepitant regimen with a multiple-day ondansetron regimen (both regimens included dexamethasone). The aprepitant regimen was found to be superior to the ondansetron regimen. The aprepitant regimen was given as follows: Aprepitant on days 1-3 of chemotherapy Ondansetron on day 1 Dexamethasone on days 1-4 This regimen is similar to the one you are using. You didn't state if the cisplatin was being given on one day or over multiple days. For multiple day, the NCCN guidelines state that dosing of aprepitant over five days (instead of the recommended three day regimen) is likely to be safe, but effectiveness has not been established. Additionally, the indication for palonosetron has been changed from once per cycle to allow for repeat dosing; again the NCCN concurs that repeat dosing is likely to be safe but data to confirm effectiveness in that setting are not available. NCCN antiemetic therapy guidelines can be accessed online at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf. Registration (free) is required to view or print NCCN guidelines.

Thank you for contacting the Expert Panel of ManageCRC.com with your question about the order of infusion for a modified FOLFOX + BEV regimen. The 5-FU bolus is given following leucovorin. The generally accepted order of administration is as follows. The references are also listed if you need further information. FOLFOX4 + Bevacizumab Leucovorin 200 mg/m2 iv over 2 hrs before 5-FU, d1 and 2 5-FU 400 mg/m2 iv bolus and then 600 mg/m2 iv over 22 hrs, d 1 and d2 Oxaliplatin (Eloxatin) 85 mg/m2 iv over 2 hrs d1 Bevacizumab (Avastin) 5-10 mg/kg iv over 30-90 min d1 Q2w Saltz LB et al. Bevacizumab (Bev) in combination with XELOX or FOLFOX4: efficacy results from XELOX-1/No 16966, a randomized phase III trial in the first-line treatment of metastatic colorectal cancer (MCRC). 2007 Gastrointestinal Cancers Symposium. Abstract 238 Giantonio, BJ et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: Results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25:1539

Thank you for your question. The National Comprehensive Cancer Network (NCCN) guidelines on colorectal cancer screening divides recommendations according to risk group. These recommendations are specific to average risk, increased risk and hereditary high-risk. The double contrast barium enema (DCBE) can be performed every 5 years in patients who are at average risk of developing colon cancer. Although DCBE is relatively sensitive and specific for detecting large neoplasms, its availability is limited. Experience with this procedure is decreasing because radiologists in training receive limited experience with this technique. Further information on the NCCN guidelines can be accessed through http://www.nccn.org, scroll down to Guidelines for Protection, Prevention and Risk Reduction and click on Colorectal Cancer Screening Guidelines. Additionally, we encourage you to consult with your family physician or gastroenterologist regarding the screening that best suits you.

Thank you for your question about colon cleansing. There are no over-the-counter preparations with cleansing properties proven to be equivalent to TriLyte. The prescribing physician or advance practice nurse (APN) should be consulted about alternates for pre-procedure colon cleansing, so we encourage you to check to see if another preparation is acceptable.

Thank you for seeking information through ManageCRC.com. The full prescribing information for Camptosar (irinotecan) available at http://www.pfizeroncology.com/products/camptosar_pi.aspx states that no additional drugs should be added to the Camptosar infusion solution (page 37). Furthermore, the manufacturer recommends that the sequence of administration should be Camptosar, followed by leucovorin, followed by 5-FU (page 32). While practices may vary in different hospitals or practice sites, the Panel must stay within the manufacturer's published recommendations.

Thanks for your question to the Expert Panel. Their reply follows. Although there has been a considerable amount of anecdotal information supporting the use of vitamin B6 (pyridoxine) to prevent or treat hand foot syndrome secondary to capecitabine, a recent prospective, phase III, placebo-controlled study reported at the American Society of Clinical Oncology (ASCO) meeting in June 2007 showed that vitamin B6 at a dose of 200mg PO daily was no better than placebo at controlling this side effect. Based on this study information, we cannot recommend the use of vitamin B6 for hand-foot syndrome. Please refer to the section in this website,under Side Effect/Symptom Management, or to the Xeloda package insert for suggestions on management of hand-foot syndrome. Reference: Lee, et al. J Clin Oncol. 2007; 25(18S), abstract 9007 To find the abstract go to http://www.asco.org/portal/site/ASCO Click on abstracts/virtual meeting in the left column Click on Abstracts In the drop down box click on 2007 ASCO Annual Meeting Find Patient Care Click on Supportive Care Click on title of Abstract #9007 Note that slides or video are available for viewing this abstract. Our best as you care for patients with CRC.

Thanks again for your inquiry. Thanks also for letting us know you are new to oncology nursing. That is helpful in forming a reply. For starters, are you a member of the Oncology Nursing Society(ONS)? Their publications offer excellent clinical information as a benefit of membership. To access those publications you need to be a member. They have a newsletter, ONS Connect, available free for all. In the January 2007 issue was a brief article on extravasation that includes a chart of Vesicant Chemotherapuetic Agents. You can access it by copying this URL and pasting it into your browser. http://www.ons.org/publications/journals/connect/pdf/2201.pdf It will take you to the newsletter, click on January 2007 and go to page 19. The above summary was based on a 2-part article that appeared in an ONS Publication: Oncology Nursing Forum, November 2006 (Vol 33. No.6): Vesicant Extravasation Part 1: Mechanisms, Pathogenesis and Nursing Care to Reduce Risk and Vesicant Extravasation Part II: Evidence-Based Management and Continuing Controversies. Another article titled Managing Extravasations is found in the Clinical Journal of Oncology Nursing, (CJON)August 2005, Vol 9, No.4. CJON is another ONS publication with a clinical focus. Please let us know if you need additional information or assistance. Regards, Expert Panel

This question sparked a discussion between the Panel members regarding the recognized need for more detailed information and guidelines regarding the administration of intravenous magnesium sulfate for other conditions, including chemotherapy-induced diarrhea (either general or caused by EGFR inhibitors). However, because of the lack of published information on this subject, the Panel feels that we must recommend the current FDA approved information regarding appropriate administration of magnesium sulfate for hypomagnesemia. These guidelines (available at www.drugs.com) call for the dosage to be adjusted specifically to the patient and response, with discontinuation of the magnesium once repletion has been achieved. Although both intravenous and intramuscular routes can be used, the intravenous dose usually obtains a therapeutic level quickly and the injection rate should not exceed 150 mg/minute except in emergency situations such as eclampsia. For mild magnesium deficiency, the adult dose is usually 1 gram, equivalent to 8.12 mEq of magnesium. A total dose of 5 g (approximately 40 mEq) can be added to 1 L of 5% Dextrose Injection USP or 0.9% Sodium Chloride Injection USP for slow intravenous infusion over a 3-hour period. Kasper and colleagues recommend oral replacement in divided doses for mild magnesium deficiency totaling 20-30 mmol/day, however diarrhea may occur, therefore this would not be a preferable route for a patient suffering CID (2005). A continuous infusion of magnesium chloride intravenously may also be used over a 24 hour period for significant deficiency, with doses reduced for patients with renal insufficiency (Kasper et al). A review of hypomagnesemia by Novello & Blumstein recommended an adult intravenous dose of 2-4 grams of 50% magnesium sulfate (16.6-33.3 mEq) diluted in saline or dextrose over 30-60 minutes. The magnesium-wasting phenomenon associated with administration of EGFR inhibitor monoclonal antibodies used in the treatment of mCRC, and although the mechanism of action is unknown, can be significant in some patients. In one recently reported study by Tejpar and colleagues, 95 out of 98 patients (97%) had decreased serum magnesium concentrations during therapy with EGFR inhibitor monoclonal antibodies compared with baseline measurements (2007). The researchers concluded that the antibodies affected the renal magnesium retention capacity and recommended that clinicians consider the risks and benefits of therapy in this population of patients. FDA Professional Drug Information database (2007). Accessed June 21, 2007 from: http://www.drugs.com/pro/magnesium-sulfate.html. Novello & Blumstein (2007). Hypomagnesemia. EMedicine. Accessed June 21, 2007 from http://www.emedicine.com/emerg/topic274.htm. Kasper, D.L., Braunwald, E., Fauci, A.S., Hauser, S.L., Longo, D.L. & Jameson, J.L. (2005). Hypercalcemic, hypocalcemic disorders in D.L. Kasper, E. Braunwald, A.S. Fauci, S.L. Hauser, D.L. Longo, & J.L. Jameson (eds.) 16th ed. Harrison’s Manual of Medicine, p. 851. Tejpar, S., Piessevaux, H., Claes, K., Piront, P., Hoenderop, J.G., Verslype, C. et al. (2007). Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study. Lancet Oncology, 8, 366-7.

Nurses caring for patients during blood transfusions must follow the guidelines, policies and procedures of their individual institution. At the minimum, the following procedures must be implemented when transfusing blood:

1. Verify that the procedure has been explained to the patient and the signed informed consent document is in the chart
2. Verify the patient's identity, following your institution's requirements for identification.
3. Checking the blood group and unit number on the blood bag against the blood group and the unit number on the transfusion slip
4. Verify the blood code or number

In most instances, two clinicians must check this information and are then are responsible for signing the transfusion form and placing the form in the medical record. Obtain vital signs before beginning the transfusion and at the intervals required by the institution policy. Document all vital signs in the medical record as well as any adverse events that occur during or following transfusion. Transfusions for cancer patients require the use of irradiated or leuko-reduced blood products. A comprehensive discussion of transfusion procedures is beyond the scope of ManageCRC.com. An excellent article addressing the immunological and infection risk issues of blood transfusion is:

"Infectious and immunologic consequences of blood transfusion"
Dellinger, EP & Anaya, DA
Critical Care 2004;8(suppl 2):S18-S23.
Available fulltext at http://ccforum.com/content/8/S2/S18.

While we don't have any details on the setting in which your patient is receiving FOLFOX (metastatic or adjuvant) or the patient's baseline ANC or platelet count, it is the collective opinion of the Expert Panel that oxaliplatin should not be administered at this time to a patient with the ANC and platelet count described in the question. The prescribing information (PI) guidelines for administration of oxaliplatin (Eloxatin) should be followed. The PI can be found online at http://www.eloxatin.com or through your infusion pharmacy. The next dose should be delayed until neutrophils ¡Ý1500 and platelets ¡Ý75k. This patient has grade 3 neutropenia and grade 2 thrombocytopenia per CTCAE ver 3.0 (http://ctep.cancer.gov/forms/CTCAEv3.pdf). (You may have to type the URL and the information is on page 4). The instructions for dose modification for grade 4 neutropenia or grade 3/4 thrombocytopenia in the adjuvant setting is to reduce the oxaliplatin dose to 75mg/m² and reduce 5-FU by 20% (300mg/m² bolus and 500mg/m² infusion). In the metastatic setting, reduce oxaliplatin to 65mg/m² and reduce 5-FU by 20% (300mg/m² bolus and 500mg/m² infusion). A table with the dose modification can be found at http://www.eloxatin.com/hcp/dosage_and_administration/default.aspx.

"Although we (Expert Panel) have limited experience with the UGT1A1 test, we suggest you contact the folks that conduct the test or review the shipping information on the site." Here is the link: http://www.genzymegenetics.com/testmenu/cancer/gene_p_testmenu_can_spechand.asp

The package insert for Avastin (bevacizumab) states that only 0.9% normal saline should be used to reconstitute Avastin for administration. Per a telephone call this morning to a medical liaison at Genentech, the manufacturer of Avastin, dextrose inactivates bevacizumab, therefore it should not be used as a diluent, nor should dextrose-containing solutions (hydration, other medications) be infused concurrently with Avastin. The following text is from the Avastin prescribing information, available at www.avastin.com:

"Preparation for Administration AVASTIN should be diluted for infusion by a healthcare professional using aseptic technique. Withdraw the necessary amount of AVASTIN to obtain the required dose and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Discard any unused portion left in a vial, as the product contains no preservatives. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Diluted AVASTIN solutions for infusion may be stored at 2-8°C (36-46°F) for up to 8 hours. No incompatibilities between AVASTIN and polyvinylchloride or polyolefin bags have been observed. AVASTIN infusions should not be administered or mixed with dextrose solutions."

You should contact the healthcare provider who gave you the instructions for your colonoscopy prep procedure. In general, instructions for Trilyte state that if you have been having clear (colored water, no solid matter) bowel movements after having consumed half of the Trilyte solution, you may stop the Trilyte. Feeling nauseated or gagging while drinking the solution is a common side effect. Chilling the solution may make it more tolerable. You should take all of the Dulcolax prescribed by your healthcare provider.

Large bowel obstruction is a common presentation among cancer patients, including those with non-colorectal malignancies. Traditionally malignant bowel obstruction is treated with surgery. In the last decade, creation of an ostomy could be completed with minimally invasive surgery, which reduces morbidity, mortality, and recovery time. In the last several years, endoscopically inserted colorectal stents have emerged as an option for palliative treatment. This involves a simple procedure, often completed on an outpatient basis. This allows the intestinal lumen to remain open without the need for surgery.¹

Another option for management of refractory pain and/or nausea is the synthetic somatostatin-analogue octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions. Octreotide is usually given subcutaneously at 50 to 200 mcg three times per day.² The role of corticosteriods in treating bowel obstruction is still controversial, but may be useful as an adjuvant antiemetic and analgesic in this setting given as dexamethasone at a starting dose of 6 to 10 mg subcutaneously or intravenously 3 to 4 times per day.^3-4

Laval et al⁵ studied 80 cases of malignant obstruction by using a series of staged interventions:

• Stage I included treatment for 5 days with a corticosteroid, antiemetic, anticholinergic, and analgesic
• Stage II provided a somatostatin analogue if vomiting persisted
• Stage III provided a venting gastrostomy.if vomiting persisted past 3 days

Obstruction relief with symptom control was obtained by medical treatment in 29 cases and symptom control occurred alone in an additional 32 cases. Ten patients were relieved by venting gastrostomy. Symptom control without permanent nasogastric tube (NGT) placement occurred in 72 episodes (90%). Eight patients with refractory vomiting were obliged to continue the NGT until death. Fifty-eight obstruction episodes (73%) were controlled in 10 days or less. Median time before gastrostomy was 17 days. Median survival was 31 days. This series suggests that a staged protocol for the treatment of inoperable malignant bowel obstruction is highly effective in relieving symptoms.⁵

References

1. Ptok H, Meyer F, Marusch F et al. Palliative stent implantation in the treatment of malignant colorectal obstruction. Surgical Endoscopy. 2006; 20:909-914.

2. Ripamonti C, Mercadante S, Groff L, et al. Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. Journal of Pain and Symptom Management, 2000; 19:23-34.

3. Feuer DJ, Broadley KE. Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Systematic Review Steering Committee. Annals of Oncology, 1999; 10: 1035-1041.

4. Von Gunten C, Muir JC. Medical management of bowel obstruction. Journal of Palliative Medicine 2002; 5:739-740.

5. Laval G, Arvieux C, Stefani L et al. Protocol for the treatment of malignant inoperable bowel obstruction : A prospective study of 80 cases at Grenoble University Hospital Center. Journal of Pain and Symptom Management. 2006; 31:502-512.

Although the package insert for oxaliplatin states it is an irritant, not a vesicant, many clinicians consider the after effects of an oxaliplatin extravasation more in keeping with those seen with vesicants. Extravasation of oxaliplatin may sometimes cause severe local inflammation and potentially tissue necrosis. The optimal non-pharmacological management of oxaliplatin extravasation is unclear. Due to issues of concurrent peripheral sensory neuropathy, it has been suggested that warm compresses may be preferred over cool compresses. Theoretically, the use of cold compresses to manage inflammation may precipitate or worsen peripheral sensory neuropathy.

For further information and additional references, please see this website's information under Extravasation Information can also be found on the Oncology Nursing Society website. Put extravasation in the search box in the upper right.

References

Foo KF, Michael M, Toner G, et al. A case report of oxaliplatin extravasation. Ann Oncol 2003;14:961-2. Link

de Lemos ML, Walisser S. Management of extravasation of oxaliplatin. J Oncol Pharm Practice 2005; 11:159-162. Link

Collectively, the Panel does not have much experience using the Model; however one Panel member has a working knowledge of the Model. She is from the Dana-Farber Cancer Institute where technical and administrative assistance was provided to the study.

There are some limitations to this model: The accuracy of the family history reported on the test form used in the validation study could not be verified, and information about certain diagnoses was limited. However, the fact that the test order form was completed by health care professionals likely minimizes reporting erroneous diagnosis. Secondly, data collection did not allow the authors to account for family size and unaffected individuals; rather the model is depending upon crude number of affected individuals. Finally, the model only provides estimation for MLH1 and MSH2 gene mutation status and updating of the model with MSH6 analysis will be provided when sufficient data are available.

In short, strong predictors of mutations were present for colorectal cancer, especially with two or more diagnoses, or endometrial cancer, and family history (number of first-degree relatives with colorectal or endometrial cancer). The authors concluded that sensitivity (probability that a person having a disease will be correctly identified) and specificity (probability that a person not having a disease will be correctly identified) depends on the cutoff used for the predicted risk. If 5% was used many patients would be considered for testing with a high sensitivity of 94% but a low specificity of 29%. But if a higher predicted risk is used (i.e. 40%), specificity would be better (92%) but many pts would be missed with a lower sensitivity of 29%. The message is, although specificity is lower with the 5% cutoff, it is safe to assume these patients should be referred for testing.

Additional information is available in:

Balmaña et al. Prediction of MLH1 and MSH2 mutations in Lynch Syndrome. JAMA, September 27, 2006;24: 1469-1478.

The Expert Panel reply is based on review of the clinical trial literature and individual practice. Some of the clinical trial literature shows giving the monoclonal first, then chemo. This is recommended in clinical practice, also.

Per the prescribing information, the recommendation for observation is a one-hour period, with the potential for longer observation if there are problems. There are no data to support shorter observation times. Late reactions after several treatments have occurred. We know that practices differ and nurses have (in the past) shortened the time. Without data to suggest shortening the time, the Panel supports the 1 hour waiting time.

More...

Thanks for the answer about the waiting time. I was also wondering about the sequence of administration when given with traditional chemotherapy. Can the Erbitux be given first followed by for example FOLFOX and the observation period occur during the chemo administration?

The Panel, with loads of experience with this combination of agents, suggest the following:

ERBITUX® (Cetuximab) is indicated for the treatment of EGFR-expressing, metastatic colorectal carcinoma:

In combination with irinotecan for patients who are refractory to irinotecan-based chemotherapy As a single agent for patients who are intolerant to irinotecan-based therapy.

The current indication is that the drug is not to be given with FOLFOX per Bristol Myers Squibb and ImClone. Of course, health care providers do different things in practice. However, the NCCN guidelines call for cetuximab in the following setting:

Indicated in combination with irinotecan-based therapy for patients refractory to irinotecan-based chemotherapy or as single agent therapy for patients intolerant to irinotecan.

The cetuximab could be given first, then followed by the irinotecan, during which time observation could take place.

http://www.nccn.org/professionals/physician_gls/PDF/colon.pdf

http://www.erbitux.com/erbitux/hcp/home/index.jsp?BV_UseBVCookie=Yes

Panitumumab (Vectibix®, Amgen, Thousand Oaks CA) was approved by the FDA on September 27, 2006 for treatment of metastatic colorectal cancer following progression on fluoropyrimidines, irinotecan and oxaliplatin. The approval was based on statistically significant prolonged progression free survival (96 days v 60 days) in patients receiving panitumumab compared to best supportive care (BSC).

Panitumumab is a fully humanized monoclonal antibody (MAb) active against the epidermal growth factor receptor (EGFR). Because it is a fully humanized MAb, hypersensitivity and infusion reaction are less likely to occur than in MAbs that include some mouse antibody. However, infusion reactions can still occur so nurses need to monitor patients carefully during the first few infusions.

In the pivotal clinical trial, panitumumab was not given in combination with chemotherapy. Patients in the pivotal study were required to have confirmed EGFR overexpression; these are the only patients for whom a benefit was shown, therefore, confirmatory testing for EGFR overexpression is recommended before initiating panitumumab therapy.

Black box (severe or life-threatening) warnings include:

• Dermatologic side effects were reported in 89% of patients receiving panitumumab and 12% of those toxicities were considered severe
• Severe infusion reactions/HSR were reported in 1% of patients receiving panitumumab

Common side effects to panitumumab include skin rash, acneiform dermatitis, electrolyte disturbances (hypomagnesemia/hypocalcemia), paronychia, diarrhea, constipation, nausea, abdominal pain and fatigue. Other side effects include pulmonary fibrosis, and potential fetal death.

The recommended dose of panitumumab is 6mg/kg administered over 60 minutes as an IV infusion every 14 days. Do not administer as an IV push or bolus. Doses higher than 1000mg should be administered over 90 minutes. No test dose or titration is needed. It should be administered using a low-protein binding 0.2 micrometer or 0.22 micrometer inline filter. It must be administered via infusion pump either by peripheral or central line. The line should be flushed before and after panitumumab administration with 0.9% sodium chloride injection to avoid mixing with other drug products or IV solutions. It should not be mixed with or administered as an infusion with other medicines and no other medications should be added to solutions containing panitumumab.

Infusion reactions were severe in approximately 1% of patients during administration of panitumumab, no fatal reactions. Reports included anaphylactic reaction, bronchospasm, fever, chills, and hypotension. The infusion should be stopped if a severe infusion reaction occurs. Depending on the severity and/or persistence of the reaction, permanently discontinue panitumumab (see dose modifications.)

Skin related toxicities were reported in 90% of patients taking panitumumab and were considered severe in 15% of patients. Ocular toxicities were reported in 15% and generally included conjunctivitis, ocular hyperemia, increased tearing and eye/eyelid irritation. Stomatatitis and oral mucositis also occurred. 25% of patients experienced paronychia with 2% of paronychia considered severe.

Dermatologic toxicity: Withhold or discontinue panitumumab and monitor for inflammatory or infectious sequelae in patients with severe dermatologic or ocular symptoms. Sun exposure may exacerbate dermatologic reactions; patients should be counseled to use sunscreen and wear protective clothing.

Dose modifications

Infusion reactions

• Reduce infusion rate by 50% in patients experiencing a grade 1 or 2 (mild or moderate) infusion reaction for the duration of that infusion
• Immediately and permanently discontinue panitumumab infusion in patients experiencing grade 3 or 4 (severe) infusion reactions


Dermatologic toxicity


• Withhold panitumumab for dermatologic toxicities grade 3 or higher or are considered intolerable. If toxicity does not improve to  grade 2 within 1 month, permanently discontinue panitumumab
• If dermatologic toxicity improves to  grade 2, and the patient is symptomatically improved after withholding no more than 2 doses of panitumumab, treatment may be resumed at 50% of the original dose.
• If toxicities recur, permanently discontinue panitumumab
• If toxicities do not recur, subsequent doses of panitumumab may be increased by increments of 25% of the original dose until the recommended dose of 6mg/kg is reached.

Nursing interventions

• Observe patient carefully during the first several infusions for development of infusion reaction or HSR
• Monitor electrolytes during and for 8 weeks after completion of panitumumab therapy
• Patients need to be instructed on ocular and skin changes, and the importance of reporting dyspnea

Further information on panitumumab can be found in the full prescribing information at http://www.amgen.com/pdfs/products/vectibix_pi.pdf

Reference:

Vectibix prescribing information. Available at http://www.amgen.com/pdfs/products/vectibix_pi.pdf Accessed October 4, 2006.

Update: Senate Bill 1955 Voted Down

In May of this year, the Senate blocked the controversial bill known as The Health Insurance Marketplace Modernization and Affordability Act of 2005 (HIMMA). The bill would allow small businesses, across state lines, to join in purchasing health insurance at affordable rates and is thought to be one way to address the problem of the uninsured. Opponents are concerned that the bill would allow the new coalitions to bypass state-mandated benefits, coverage, and rules thereby eliminating consumer protection for health care. They cite loss of coverage for prenatal, maternal care, immunizations, diabetes coverage, cervical and colorectal screenings, and mammograms to name a few. Additionally, access to providers of care would be cut. The full Senate report suggests that versions of this bill have been around since the 1970s. Although voted down in May, another version of the bill is expected to appear in the next Congress.

Thank you for your question. Our Expert Panel has looked into the issue of using calcium and magnesium for management of oxaliplatin-related neuopathy. That information can be found on the www.ManageCRC.com website in the section on Side Effect and Symptom Management/Neurotoxicity. The following link will take you directly to that page: http://www.managecrc.com/html/side-effect-neurotoxicity.asp Due to the lack of clinically-proven data from prospective randomized clinical trials of oral calcium/magnesium supplementation to manage neurotoxicity, no dosing recommendation can be made by our Expert Panel at this time.

Good news may be around the corner, however! An abstract presented at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer meeting in January 2006 discussed a promising new oral drug, xaliproden, for management of neuropathy induced by oxaliplatin. The oral presentation and abstract information follow as the close of this message.

Thank you for submitting your question to ManageCRC.com! Should you have any further questions, please feel free to post another question to the website.

Oral presentation and abstract information:

ORAL PRESENTATION
Saturday, January 28, 2006 1:00 PM (PST)
Lead Author: James Cassidy, MD, MSc, Glasgow University

Xaliproden Reduces Neuropathy Associated with Oxaliplatin

A new phase III study has shown that the drug xaliproden (Xaprila) reduced the frequency of neuropathy, a common side effect of the chemotherapy drug oxaliplatin, without altering the effectiveness of the FOLFOX therapy being given to patients with colorectal cancer. FOLFOX (a combination of the chemotherapy drugs oxaliplatin, fluorouracil, and leucovorin) recently became a standard therapy for patients with advanced colorectal cancer.

"The research community has been seeking ways to combat the neurotoxic effects of oxaliplatin in order to use this drug to even greater effect, most notably for colorectal cancer, said James Cassidy, MD, MSc, Cancer Research UK Professor of Oncology at Glasgow Universi ty in Scotland, and lead author of the study. Our research supports this effort by showing that xaliproden reduces nerve problems in patients receiving oxaliplatin"

Peripheral sensory neuropathy, a side effect of oxaliplatin, can cause numbness, tingling, and burning, particularly in the arms, hands, legs, and feet. More than 90% of patients receiving FOLFOX have reported experiencing these symptoms at some point during their treatment, with more than 10% reporting severe symptoms. Xaliproden is taken orally, and is currently used to treat patients with amyotrophic lateral sclerosis (Lou Gehrig's disease).

Researchers compared the incidence of severe neuropathy in 325 patients with metastatic colorectal cancer who received daily xaliproden along with FOLFOX treatment, and 324 patients who received FOLFOX alone. Severe peripheral sensory neuropathy was reported by 16.7% of patients in the FOLFOX group compared with 11.1% of patients who received FOLFOX plus xaliproden.

Dr. Cassidy and colleagues noted that they are planning a larger clinical trial to extend and confirm their findings.

Abstract # 229
Randomized double blind (DB) placebo (Plcb) controlled Phase III study assessing the efficacy of Xaliproden (X) in reducing the cumulative peripheral sensory neuropathy (PSN) induced by the oxaliplatin (Ox) and 5-FU/LV combination (FOLFOX4) in 1st line treatment of patients (pts) with metastatic colorectal cancer
J. Cassidy, G. A. Bjarnason, T. Hickish, C. Topham, M. Provencio, G. Bodoky, L. Landherr, P. Koralewski, G. Lopez-Vivanco, G. Said

Background: X, an orally administered non-peptide neurotrophic agent developed by sanofi-aventis, was shown in vitro to minimize neuritic damage induced by Ox (co-culture of Schwann cells and dorsal roots ganglia explant). The probability of occurrence of Grade (Gr) 3-4 PSN at a cumulative dose of Ox of 1000 mg/m², was consistently reported to be of 18-20%. Methods: First line MCRC pts were randomized to receive, in a DB fashion, FOLFOX4 and either Plcb or X 1mg daily. X was administered from the 1st day of chemotherapy till 15 days post last Ox cycle. Co-primary objectives were reduction in the risk of occurrence of Gr 3-4 PSN relative to cumulative dose of Ox (Kaplan-Meier method) and non-inferiority in response rate (RR). Secondary endpoints included evaluation of sensory action potential (SAP) and safety. Results: From July 2002 to May 2004, 649 pts were randomized (324 Plcb, 325 X). Pts characteristics were well balanced across arms, median number of Ox cycles was 12 in both arms, median relative dose intensity (%) was 83.8 (Plcb) and 85.2 (X). A significant risk reduction of 39% in the probability of Grade 3-4 PSN in favor of X was reported (hazard ratio [95% CI] = 0.61 [0.40; 0.93], p= 0.0203). Overall RR [95 % CI] was: Plcb 42.6% [37.1; 48.2] and X 44.9% [39.4; 50.6]. As prospectively defined in the protocol, the lower bound of the CI of the RR ratio above 0.8 confirms noninferiority in RR (1.055 [0.88; 1.26]). In both arms the mean % of change in SAP worsens as a function of PSN severity. 17.3 (Plcb) and 13.5% (X) of the pts discontinued Ox because of PSN. Severe toxicities (% Gr 3-4), reported with a ≥2% difference between arms, were (plcb vs X): diarrhea 10.9 vs 13.0, pulmonary embolism 0.9 vs 3.1, fatigue 3.7 vs 1.5, neutropenia 43.0 vs 37.8. Conclusion: X was shown to be efficient in reducing the risk of Grade 3-4 oxaliplatin-induced PSN without impacting FOLFOX4 antitumor activity.

Thank you for drawing our attention to the dosage of bevacizimab 10mg/kg used with the FOLFOX4 regimen listed on the last row of the Chemotherapy Regimens table in the Resource section of the Web site. Various clinical studies report doses higher than 5mg/kg for treating different cancers. However, the FDA-approved dosage is 5 mg/kg.

The table has been adjusted to reflect the FDA-approved dosage along with two new references.

Thank you for your encouragement. Please feel free to share other concerns or ideas that will add to the usefulness of manageCRC.com

There is no consensus among the Expert Panel for the use of a “one pill prep” for a colonoscopy. The standard remains liquid preps containing liquid sodium phosphate. Diacol®, the first patented sodium phosphate purgative in tablet format is marketed in the United States under the name Visicol®. As many as 40 tablets are available for colon cleansing. The following Web site will provide you with more information: http://www.rxlist.com/cgi/generic/visicol_ids.htm

Thank you for your question. Please feel free to contact us with additional questions or ideas that will add to the usefulness of manageCRC.com

Thanks for your inquiry. Sounds like your clinical experience supports the literature that states different GI cancers are on the increase. For the present time, the Web site is focused on colorectal cancer. We encourage you to post questions related to the care of patients with CRC. Also, please feel free to give us your feedback on the usefulness of the Web site and any suggestions for improvement.

This is one of the most complex questions to answer. This is a collective response from the www.manageCRC.com Expert Panel. The Panel represents all geographic areas and broad practice areas, including home care.

Not knowing the patient’s insurance status or what resources you have contacted, our suggestions are based on our experiences through our institutions, states and/or professional associations. There is no easy one-stop solution in finding funding. We know it takes time and detective work.

If your center is a NCI-designated cancer center, we assume you have social work services and have referred the patient to them. If the problem is with co-pay, The Patient Assistance Foundation CoPay Relief program at http://www.copays.org/ can help. Their main web site is at http://www.patientadvocate.org/ Also, pharmaceutical companies can help with co-payments for their specific drugs. Those resources would depend on the therapies selected.

You might check your hospital pharmacy who may assist in finding reimbursement or “replacement” drugs for indigent patients. Check out the National Coalition for Cancer Survivors (NCCS) Financial Assistance page at http://www.canceradvocacy.org/resources/essential/financial.aspx This is an inclusive description of organizations and approaches for survivors in need of financial support. A website that covers a colorectal diagnosis is Patient Access Network Foundation at contact@patientaccessnetwork.org and www.patientaccessnetwork.org. While the American Cancer Society can provide support for smaller dollar items and other needs there are also local cancer groups. Your inquiry is a critical issue. We would be interested in the outcome as well as your journey in tracking down resources. This would benefit oncology nurses with similar issues.

Thank you for your question. There are guidelines but no absolute standards, because each “institution” should have its own management guidelines for HSRs. Institution refers to the practice setting in which chemotherapy is being provided. This could be an office or another outpatient area as well as in the home. For nurses responsible for establishing practice guidelines in any setting, without the advantage of large institutional support, the following resources may be helpful. There is no one “recipe,” and multiple resources need to be consulted to establish your guidelines. This Web site offers resources by clicking here for HSR under FAQs and here for HSR under Side Effect Symptom Management. The latter offers an algorithm for the management of HSR with the suggestion that individual institutional protocols be consulted. The Web site www.eloxatin.com offers suggestions on medications to treat HSR and is based on symptoms and institutional guidelines. An excellent reference is Hypersensitivity Reactions to Oxaliplatin: What Nurses Need To Know, by Bonosky and Miller (Clin J of Oncol Nurs. 2005; 9:325-330). The article presents etiology, manifestations, treatment, prophylaxis, and re-treatment. 

Thank you for your question. This can be confusing as well as controversial. An important first step is consulting Clinical Practice Guidelines. They contain general agreement that FOLFOX regimens offer a survival advantage over non-oxaliplatin containing regimens. However, oncologists have the option to individualize therapy. The choice often depends on the oncologist's personal experience, evaluation of the side effect profile for each regimen, health history, patient convenience, performance status, and reimbursement. The physician may make recommendations based on FOLFOX4 versus FOLFOX6, both mentioned in the National Comprehensive Cancer Network (NCCN) Guidelines. NCCN lists both FOLFOX4 and mFOLFOX6, along with FLOX as options in the adjuvant setting. Some data report higher response rates with FOLFOX7 compared with FOLFOX4. Although FOLFOX4 and 6 appear to have similar efficacies, their side effect profile is slightly different.  FOLFOX4 was approved by the FDA, while FOLFOX6 has been used more often for patient convenience.

Thank you for submitting your question to the Expert Panel of ManageCRC.com. For the first time, a question has left our Panel without clear evidence to support a particular practice that has generally been the standard in nearly all the CRC studies investigating 5-FU (e.g. deGramont, A et al. [1997]. Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with bimonthly high-dose leucovorin plus continuous infusion for advanced colorectal cancer: A French intergroup study. Journal of Clinical Oncology 15:808-815) We are assuming you are referring to the deGramont or LV5FU2 regimen. Subscription required for full article. Abstract is free at this link: http://jco.ascopubs.org/cgi/content/abstract/15/2/808 We had thought it might be an issue of 5-FU pharmacokinetics. Although we found several papers discussing the pharmacokinetics of infusional 5-FU vs oral 5-FU, nothing was found suggesting that 5-FU pharmacokinetics in the LV5FU2 regimen was the reason for starting the continuous infusion within 1 hour of completing the bolus administration. Another thought was pharmacokinetics of the 2-hour leucovorin infusion that is given prior to the 5-FU bolus, that is, starting the 5-FU continuous infusion while leucovorin is still active. We will continue to research your question and will advise you if outside sources can lend a hand with this issue. Stay tuned!

While we don't have any details on the setting in which your patient is receiving FOLFOX (metastatic or adjuvant) or the patient's baseline ANC or platelet count, it is the collective opinion of the Expert Panel that oxaliplatin should not be administered at this time to a patient with the ANC and platelet count described in the question. The prescribing information (PI) guidelines for administration of oxaliplatin (Eloxatin) should be followed. The PI can be found online at http://www.eloxatin.com or through your infusion pharmacy. The next dose should be delayed until neutrophils ¡Ý1500 and platelets ¡Ý75k. This patient has grade 3 neutropenia and grade 2 thrombocytopenia per CTCAE ver 3.0 (http://ctep.cancer.gov/forms/CTCAEv3.pdf). (You may have to type the URL and the information is on page 4). The instructions for dose modification for grade 4 neutropenia or grade 3/4 thrombocytopenia in the adjuvant setting is to reduce the oxaliplatin dose to 75mg/m² and reduce 5-FU by 20% (300mg/m² bolus and 500mg/m² infusion). In the metastatic setting, reduce oxaliplatin to 65mg/m² and reduce 5-FU by 20% (300mg/m² bolus and 500mg/m² infusion). A table with the dose modification can be found at http://www.eloxatin.com/hcp/dosage_and_administration/default.aspx.

The package insert for Avastin (bevacizumab) states that only 0.9% normal saline should be used to reconstitute Avastin for administration. Per a telephone call this morning to a medical liaison at Genentech, the manufacturer of Avastin, dextrose inactivates bevacizumab, therefore it should not be used as a diluent, nor should dextrose-containing solutions (hydration, other medications) be infused concurrently with Avastin. The following text is from the Avastin prescribing information, available at www.avastin.com:

"Preparation for Administration AVASTIN should be diluted for infusion by a healthcare professional using aseptic technique. Withdraw the necessary amount of AVASTIN to obtain the required dose and dilute in a total volume of 100 mL of 0.9% Sodium Chloride Injection, USP. Discard any unused portion left in a vial, as the product contains no preservatives. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Diluted AVASTIN solutions for infusion may be stored at 2-8°C (36-46°F) for up to 8 hours. No incompatibilities between AVASTIN and polyvinylchloride or polyolefin bags have been observed. AVASTIN infusions should not be administered or mixed with dextrose solutions."

Nurses caring for patients during blood transfusions must follow the guidelines, policies and procedures of their individual institution. At the minimum, the following procedures must be implemented when transfusing blood:

1. Verify that the procedure has been explained to the patient and the signed informed consent document is in the chart
2. Verify the patient's identity, following your institution's requirements for identification.
3. Checking the blood group and unit number on the blood bag against the blood group and the unit number on the transfusion slip
4. Verify the blood code or number

In most instances, two clinicians must check this information and are then are responsible for signing the transfusion form and placing the form in the medical record. Obtain vital signs before beginning the transfusion and at the intervals required by the institution policy. Document all vital signs in the medical record as well as any adverse events that occur during or following transfusion. Transfusions for cancer patients require the use of irradiated or leuko-reduced blood products. A comprehensive discussion of transfusion procedures is beyond the scope of ManageCRC.com. An excellent article addressing the immunological and infection risk issues of blood transfusion is:

"Infectious and immunologic consequences of blood transfusion"
Dellinger, EP & Anaya, DA
Critical Care 2004;8(suppl 2):S18-S23.
Available fulltext at http://ccforum.com/content/8/S2/S18.

Large bowel obstruction is a common presentation among cancer patients, including those with non-colorectal malignancies. Traditionally malignant bowel obstruction is treated with surgery. In the last decade, creation of an ostomy could be completed with minimally invasive surgery, which reduces morbidity, mortality, and recovery time. In the last several years, endoscopically inserted colorectal stents have emerged as an option for palliative treatment. This involves a simple procedure, often completed on an outpatient basis. This allows the intestinal lumen to remain open without the need for surgery.¹

Another option for management of refractory pain and/or nausea is the synthetic somatostatin-analogue octreotide. This agent inhibits the release of several gastrointestinal hormones and reduces gastrointestinal secretions. Octreotide is usually given subcutaneously at 50 to 200 mcg three times per day.² The role of corticosteriods in treating bowel obstruction is still controversial, but may be useful as an adjuvant antiemetic and analgesic in this setting given as dexamethasone at a starting dose of 6 to 10 mg subcutaneously or intravenously 3 to 4 times per day.^3-4

Laval et al⁵ studied 80 cases of malignant obstruction by using a series of staged interventions:

• Stage I included treatment for 5 days with a corticosteroid, antiemetic, anticholinergic, and analgesic
• Stage II provided a somatostatin analogue if vomiting persisted
• Stage III provided a venting gastrostomy.if vomiting persisted past 3 days

Obstruction relief with symptom control was obtained by medical treatment in 29 cases and symptom control occurred alone in an additional 32 cases. Ten patients were relieved by venting gastrostomy. Symptom control without permanent nasogastric tube (NGT) placement occurred in 72 episodes (90%). Eight patients with refractory vomiting were obliged to continue the NGT until death. Fifty-eight obstruction episodes (73%) were controlled in 10 days or less. Median time before gastrostomy was 17 days. Median survival was 31 days. This series suggests that a staged protocol for the treatment of inoperable malignant bowel obstruction is highly effective in relieving symptoms.⁵

References

1. Ptok H, Meyer F, Marusch F et al. Palliative stent implantation in the treatment of malignant colorectal obstruction. Surgical Endoscopy. 2006; 20:909-914.

2. Ripamonti C, Mercadante S, Groff L, et al. Role of octreotide, scopolamine butylbromide, and hydration in symptom control of patients with inoperable bowel obstruction and nasogastric tubes: a prospective randomized trial. Journal of Pain and Symptom Management, 2000; 19:23-34.

3. Feuer DJ, Broadley KE. Systematic review and meta-analysis of corticosteroids for the resolution of malignant bowel obstruction in advanced gynaecological and gastrointestinal cancers. Systematic Review Steering Committee. Annals of Oncology, 1999; 10: 1035-1041.

4. Von Gunten C, Muir JC. Medical management of bowel obstruction. Journal of Palliative Medicine 2002; 5:739-740.

5. Laval G, Arvieux C, Stefani L et al. Protocol for the treatment of malignant inoperable bowel obstruction : A prospective study of 80 cases at Grenoble University Hospital Center. Journal of Pain and Symptom Management. 2006; 31:502-512.

Thank you for seeking information through ManageCRC.com. The full prescribing information for Camptosar (irinotecan) available at http://www.pfizeroncology.com/products/camptosar_pi.aspx states that no additional drugs should be added to the Camptosar infusion solution (page 37). Furthermore, the manufacturer recommends that the sequence of administration should be Camptosar, followed by leucovorin, followed by 5-FU (page 32). While practices may vary in different hospitals or practice sites, the Panel must stay within the manufacturer's published recommendations.

Thanks again for your inquiry. Thanks also for letting us know you are new to oncology nursing. That is helpful in forming a reply. For starters, are you a member of the Oncology Nursing Society(ONS)? Their publications offer excellent clinical information as a benefit of membership. To access those publications you need to be a member. They have a newsletter, ONS Connect, available free for all. In the January 2007 issue was a brief article on extravasation that includes a chart of Vesicant Chemotherapuetic Agents. You can access it by copying this URL and pasting it into your browser. http://www.ons.org/publications/journals/connect/pdf/2201.pdf It will take you to the newsletter, click on January 2007 and go to page 19. The above summary was based on a 2-part article that appeared in an ONS Publication: Oncology Nursing Forum, November 2006 (Vol 33. No.6): Vesicant Extravasation Part 1: Mechanisms, Pathogenesis and Nursing Care to Reduce Risk and Vesicant Extravasation Part II: Evidence-Based Management and Continuing Controversies. Another article titled Managing Extravasations is found in the Clinical Journal of Oncology Nursing, (CJON)August 2005, Vol 9, No.4. CJON is another ONS publication with a clinical focus. Please let us know if you need additional information or assistance. Regards, Expert Panel