Case Study (1/2)
Adjuvant Case Study: Colorectal Cancer
M.B. is a 65-year-old African-American man who presented to his primary care physician with the chief complaint of intermittent abdominal pain and constipation symptoms for approximately 2 months. He initially attributed his symptoms to his diet and subsequently underwent colonoscopy, which revealed a 4.5-cm nonobstructing mass in the transverse colon. CT scans of the chest, abdomen, and pelvis did not demonstrate evidence of metastatic disease. The carcinoembryonic antigen (CEA) level at the time of surgery was 5.0. The patient underwent a transverse colectomy which revealed a mass invading through the muscularis propria into the subserosa, with 6 positive regional lymph nodes and no evidence of metastases. Final pathology revealed a moderately differentiated adenocarcinoma.
Past medical history: Hyperlipidemia, hypertension, osteoarthritis, diabetes.
Past surgical history: total right knee replacement in 2002.
Family history: no family history of colorectal cancer. M.B.'s father deceased from lung cancer at age 70.
Social history: M.B. is retired, married, and the father of 2 grown children, a son and a daughter. He does not smoke cigarettes, but drinks 2 beers per day. He denies illicit drug use.
No known drug, food, or environmental allergies.
Current medications: glyburide 2.5 po bid, atenolol 50 mg po daily, Zestril 10 mg po daily, acetaminophen prn as directed.
Treatment options were discussed with M.B., which included an adjuvant regimen of 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (FOLFOX 6) for a planned 12 cycles of therapy following complete recovery from surgery. The patient was initiated on a course of oxaliplatin 85 mg/m2 over 2 hours on day 1, with leucovorin 200 mg/m2 over 2 hours, 5-FU 400 mg/m2 IV bolus, then 2.4 g 5-FU over 46 hours , by continuous infusion repeated every 2 weeks. He was given Decadron 10mg po and Zofran 16mg po prior to the initiation of cycle #1, for nausea prophylaxis. Additionally, he was discharged home from the clinic with a prescription for Zofran 8 mg po q 8 hours x 48-72 hours following treatment and then q 8hours prn as needed for nausea or vomiting. He was instructed on the use of Imodium 2 tablets at the first sign of diarrhea, then 1 capsule every 2 hours during the day, 2 capsules at bedtime and every 4 hours until morning. He was instructed to stop taking Imodium A-D when he has not had a bowel movement for 12 hours. Potential side effects of Zofran and Imodium A-D were reviewed with the patient. He verbalizes understanding. He was instructed to contact our office for fever 100.5 or >, nausea, vomiting, or diarrhea refractory to current treatment plan if symptoms persistent longer than 24 hours or for any questions, problems or concerns. He will return to the clinic in two weeks for reevaluation.
Clinical questions for consideration:
- What are the risks for development of colorectal cancer? The incidence of colorectal cancer increases with age. Overall, approximately 91% of new cases occur in individuals older than 50 years. Incidence rates are approximately 35% higher in men than in women and higher in African-American men and women (American Cancer Society, 2005a). Individuals with a first-degree relative who has had colorectal cancer have an increased risk of developing the disease. This risk increases if the relative was diagnosed before age 60 (American Cancer Society, 2005a). M.B. is a 65-year-old African-American man with no family history of colorectal malignancies.
- Why was colonoscopy chosen to evaluate colonic mucosa? This procedure allows for direct visualization of the rectum and colon. Because a much longer instrument than the sigmoidoscope is used, the physician can view the entire colon. This test is considered the most highly sensitive for the detection of colon cancer and adenomatous polyps. It also allows for the removal of polyps, if found, at the time of the examination (American Cancer Society 2005a).
- What is the significance of preoperative CEA level? CEA levels should be routinely measured preoperatively in patients undergoing surgical resection for colon cancer. There is evidence in the literature that suggests an elevated preoperative CEA level is a poor prognositic indicator (Cima et al. Gastrointestinal Oncology. 2004;676-681).
- What is the cancer stage of this patient and how is it determined? M.B. has T3 N2 M0 colon cancer (stage IIIC), given the anatomic extent of lesion invading into the muscularis propria, greater than 4 positive nodes, and no evidence of distant metastases. Currently, staging for colorectal cancer is based upon radiologic and pathologic staging, thus the rationale for CT scan following colonoscopy to assess disease status and evaluate for metastatic disease (Cima et al. Gastrointestinal Oncology. 2004;676-681).
- Why is it important to review M.B.'s comorbities in this case? M.B. has been offered combination therapy with 5-FU, leucovorin, and oxaliplatin (FOLFOX6). He has a medical history significant for diabetes, osteoarthritis, hyperlipidemia, hypertension. MB has no baseline neuropathy on exam. It is important to note that Oxaliplatin is associated with neurotoxicity that can be further subdivided into two types, acute and chronic. Acute neurotoxicity generally last < 14 days, typically noted with exposure to cold, with chronic neurotoxicity lasting > 14 days, and associated with cumulative dose levels of 800mg/m2 (Wilkes et al. Clin J Oncol Nurs. 2005;9:31-44). M.B. needs to be monitored closely for the development of peripheral neuropathy, because it is also a potential complication of diabetes. It would be important to assess on history and physical if he had baseline neuropathy, in which case on might consider alternative treatment options. He has osteoarthritis. Patients receiving oxalipatin may experience muscle cramping inthe jaw, hand, or arm. Baseline assessment prior to initiation of therapy is essential.
- Why was FOLFOX chemotherapy offered to M.B. as a treatment option? Based on the MOSAIC trial, in which 2,246 patients with completely resected stage II (40%) or III (60%) colon cancer were randomly assigned to receive LV5FU2 or FOFOX4 (oxaliplatin 85 mg/m2 IV over 2 hours, day 1, LV 200 mg/m2 IV over 2 hours on days 1 and 2, 5-FU 400 mg/m2 IV bolus, then 600 mg/m2 IV over 22 hours on days 1 and 2). With a median follow-up of 4 years, a 24% reduction in relative risk of relapse was observed with the FOLFOX4 combination regimen in the overall population. In the overall population, 84.3% and 82.7 % of patients were still alive, respectively, in the FOLFOX4 and LV5FU2 arms at 4-year follow-up. The MOSAIC study demonstrated improvement in overall disease survival (de Gramont et al. J Clin Oncol. 2005;23(suppl 16):246s. Abstract 3501).
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