BECAUSE of recent advances in the treatment of metastatic

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1 36 Seminars in Oncology Nursing, Vol 23, No 1 (February), 2007: pp OBJECTIVES: To illustrate the multiple factors that can influence the treatment continuum approach. DATA SOURCES: Actual cases drawn from the authors clinical experience, scientific studies, and review articles. CONCLUSION: Patients treated for metastatic colorectal cancer (mcrc) commonly experience toxicities that oncology nurses must be aware of and ready to manage with appropriate interventions. IMPLICATIONS FOR NURSING PRACTICE: By becoming familiar with mcrc, oncology nurses will be better able to address toxicities that arise from the treatments applied. By serving as mentors and guides, oncology nurses can aid patients in self-care management and problem solving to optimize quality of life and potentially extend life. Yvonne Lassere, RN, OCN : Manager, Clinical Protocol Administration, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Robin Sommers, MS, APRN, BC, AOCNP: Oncology Nurse Practitioner, Department of Gastrointestinal Oncology, Dana-Farber Cancer Institute, Boston, MA. Pamela Hallquist Viale, RN, MS, APRN, BC, AOCNP: Oncology Nurse Practitioner, Sunnyvale, CA; Assistant Clinical Professor, Department of Physiological Nursing, University of California, San Francisco. Carol S. Viele, RN, MS: Clinical Nurse Specialist, Hematology-Oncology-Bone Marrow Transplant, University of California San Francisco Medical Center. Rita Wickham, PhD, RN, AOCN, Oncology & Palliative Care Consultant, Associate Professor, College of Nursing, Rush University Medical Center, Chicago, IL. Address correspondence to Yvonne Lassere, RN, OCN, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX Elsevier Inc. All rights reserved /07/2301-$30.00/0 doi: /j.soncn CASE STUDIES IN METASTATIC COLORECTAL CANCER YVONNE LASSERE, ROBIN SOMMERS, PAMELA HALLQUIST VIALE, CAROL S. VIELE, AND RITA WICKHAM BECAUSE of recent advances in the treatment of metastatic colorectal cancer (mcrc), patients have more choices in the initial treatment of this disease. These newer therapies have extended survival from approximately 7 months with best supportive care to as many as 24 months. Patients are gratified to learn of the multiple treatment options available to them; however, the mode of administration as well as the side-effect profile of the therapy chosen may be influenced by the patient s specific desires or comorbidities. Along with the patient s preference, the oncology nurse s assessment will contribute to the initial choice of therapy. These real-life case studies illustrate the multiple factors that can influence the treatment continuum approach, including individualized side-effect management. CASE STUDY #1: SELECTING THERAPY FOR MCRC: FOLFOX OR FOLFIRI PLUS BEVACIZUMAB Mrs B, a healthy 50-year-old African-American, began to have vague gastrointestinal symptoms, which included constipation, bloating, and occasional abdominal pain/cramping that she attributed to heartburn. Over the next several months her symptoms worsened, and she saw her primary care physician in February of She reported losing 15 pounds in the past year, which she attributed to decreased appetite and gastrointestinal symptoms. Laboratory evaluation showed grade 2 anemia (hemoglobin 9.4 g/dl) and a carcinoembryonic antigen (CEA) level of 200 ng/ml. A colonoscopy confirmed a 6-cm mass in the sigmoid colon. Subsequent chest and abdominal computed tomography (CT) scans

2 CASE STUDIES IN METASTATIC COLORECTAL CANCER 37 ruled out lung metastases but detected multiple liver lesions. The patient underwent left colectomy and was found to have a palpable tumor in the left lobe of the liver during surgery. The primary tumor had invaded the muscularis propria, extending into the subserosa, and 6 of 18 resected lymph nodes were positive for tumor. Mrs B was deemed to have T3, N2, M1 (stage IV) colon cancer. Findings included: Past medical history: diabetes, mild hypertension, and hyperlipidemia Past surgical history: wisdom teeth extracted in 1976 Family history: negative for cancer; inflammatory bowel disease, Gilbert s syndrome Social history: married, lives in a single-family home with her husband; three children, age 20, 23, and 26; college graduate, works full time as an administrative secretary; has close family and support systems in place Current medications: glyburide, 5 mg orally daily; lisinopril, 5 mg daily; atorvastin calcium, 10 mg daily No known drug, food, or environmental allergies Baseline vital signs: temperature, 98; pulse, 72; respirations, 18; blood pressure (BP), 122/60 Current laboratory values: complete blood count with differential; chemistries, including electrolytes and renal function tests, within normal limits (WNL); fasting blood glucose, 140; albumin and protein levels, WNL; alanine aminotransferase (ALT), or SGPT, 37; aspartate aminotransferase, or SGOT, 34; alkaline phosphatase, 150 (institutional parameters, ); total bilirubin, 0.3; baseline urine dipstick for protein, negative. Eastern Cooperative Oncology Group (ECOG) performance status: 1 Treatment Options and Interventions For Mrs B, the best evidence would support treatment with a regimen of 5-fluorouracil/leucovorin (5-FU/LV) plus oxaliplatin (Eloxatin; Sanofi-Aventis, Bridgewater, NJ) (the FOLFOX regimen) or 5-FU/LV plus irinotecan (Camptosar; Pfizer Inc, New York, NY) (the FOLFIRI regimen) in combination with bevacizumab (Avastin; Genentech, Inc, South San Francisco, CA). Considerations regarding treatment recommendations include: comorbid conditions (positive for diabetes, hypertension, and hyperlipidemia; negative for neuropathy, inflammatory bowel disease, liver dysfunction, or Gilbert s syndrome); physical and mental abilities needed to manage therapy (good performance status, able to manipulate infusional pump, highly educated); financial issues (has health insurance from a health maintenance organization, owns home, on medical leave); adequate social support (family willing to drive patient to appointments); current occupation (administrative secretary); and patient preference. Because she had diabetes, which may increase risk for neuropathy and because worsening neuropathy could affect functioning in her occupation as a secretary, FOLFIRI with bevacizumab was recommended to palliate metastatic disease and prolong survival. Mrs B agreed to receive four cycles of therapy and then undergo restaging. She had a double-lumen tunneled catheter surgically placed before treatment. Blood pressure and urine dipsticks were to be monitored before each treatment because of the risks of hypertension and proteinuria with bevacizumab. Five weeks following surgery her incision was healed, and Mrs B started FOLFIRI and bevacizumab every 2 weeks. Her nurse instructed her about associated side effects of each agent, and the patient verbalized that she understood. Written diarrhea management and loperamide dosing sheets were also reviewed. Mrs B developed mild abdominal cramping during the initial irinotecan infusion that resolved with atropine, 0.4 mg intravenously, and prophylactic atropine was given during subsequent cycles of the combination regimen. On follow-up 2 weeks later, she reported mild diarrhea (grade 2) on day 4 after treatment, which resolved within 24 hours use of loperamide as well as other diarrhea management recommendations (eating a bland diet consisting of such foods as plain pasta, toast, rice, and bananas; avoiding products containing lactose; and drinking eight glasses of clear liquids a day [Gatorade, Chicago, IL]). Mrs B gradually resumed her regular diet. She also developed grade 1 nausea that was controlled by ondansetron (Zofran; GlaxoSmithKline, Research Triangle Park, North Carolina), a prescribed antiemetic but reported no mucositis, fevers, weight loss, hair loss, or vomiting. After four cycles of FOLFIRI with bevacizumab, restaging CT scans demonstrated regression of liver metastases and the patient s CEA level was now 60. She continued therapy and on day 7 following the fifth cycle of combination therapy

3 38 LASSERE ET AL developed grade 3 diarrhea that did not resolve despite aggressive loperamide and other self-care measures. Mrs B was admitted to the hospital for aggressive intravenous hydration and electrolyte replacement and monitoring of glucose, electrolytes, stool cultures, and complete blood cell count. She was started on subcutaneous octreotide, 150 g 3 times daily, given for severe diarrhea, as well as on a fluoroquinolone antibiotic. 1 Her symptoms resolved within 24 hours, and she was discharged on day 3. The sixth cycle of FOLFIRI plus bevacizumab was delayed 1 week and then resumed with a 25% reduction in the dose of irinotecan. Discussion Tournigand et al 2 found that a regimen of FOLFOX followed by FOLFIRI had a similar median survival rate and efficacy in patients with advanced CRC as FOLFIRI followed by FOLFOX, a finding that informed the clinicians choice of therapy in this case. When the oncology team reviewed treatment options with Mrs B and her husband, several factors in the patient s history guided the clinical recommendations, including her functional status, comorbid conditions, preferences, occupation, socioeconomic status, and the social support systems available to her. Vigilant assessment is critical throughout the treatment continuum. Nurses must accurately assess baseline bowel habits and reassess before each subsequent treatment. Patient and family education about early recognition of toxicities are key to successful management, and pharmacologic and nondrug measures may be helpful in successfully managing diarrhea. Early recognition of adverse events may also minimize the effect on the patient s quality of life while helping to prevent lifethreatening sequelae. Summary of Key Points Consideration should be given to the patient s underlying coexisting conditions when determining the optimal sequence of chemotherapy regimens. Oncology nurses play a crucial role in performing a comprehensive assessment that takes into account the patient s functional status, comorbidities, social supports, and cognitive, emotional, and financial status. Patient and family education are key to early recognition and successful management of diarrhea symptoms. CASE STUDY #2: FRONTLINE THERAPY FOR METASTATIC COLORECTAL CARCINOMA: FOLFOX WITH BEVACIZUMAB OR FOLFOX ALONE Mrs K, a 46-year-old, had a 6-month history of bright red blood per rectum when she sought medical treatment after experiencing severe cramping and bloody diarrhea. She underwent a colonoscopy, which demonstrated an obstructive lesion in her sigmoid colon at 19 cm. Her CEA level was normal (1.1 ng/ml), as were her liver and renal function tests, but a CT scan of the abdomen demonstrated an 8-cm lesion in the liver that was deemed unresectable. The patient was admitted to the hospital for a laparoscopic sigmoid colectomy. Pathology demonstrated an infiltrating and poorly differentiated adenocarcinoma. The tumor penetrated through the muscularis propria into the pericolonic adipose tissue. Fifteen of 15 lymph nodes were positive for tumor, and Mrs K s cancer was diagnosed as stage IV disease (T4, N2, M1). Findings included: Past medical history: rosacea Past surgical history: appendectomy at age 24 Family history: father died at age 62 with cancer of unknown origin Social history: married with 2 children, ages 22 and 20; good family support Current medications: metronidazole gel (Metro- Gel; 3M Healthcare, St Paul, MN), 0.075% daily No known drug, food, or environmental allergies Current laboratory values: all WNL ECOG performance status: 0 Treatment Options and Interventions Chemotherapeutic options were discussed in detail. These included FOLFOX with or without bevacizumab, FOLFIRI with or without bevacizumab, capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) alone, or entering a clinical trial. The patient was reluctant to receive any chemotherapy. Only after much discussion with her family and a delay of 2.5 months did she begin therapy with FOLFOX plus bevacizumab. Mrs K was instructed on possible toxicities, including neuropathy (acute and chronic), neutropenia, thrombo-

4 CASE STUDIES IN METASTATIC COLORECTAL CANCER 39 cytopenia, pharyngolaryngeal dysesthesia, and diarrhea. 3 A central venous access device was placed to facilitate chemotherapy administration. After her first cycle of therapy in clinic, Mrs K drank a cold beverage and immediately had the sensation of not being able to breathe. The feeling resolved fairly quickly and without intervention. She was assured by her primary oncology nurse that this was a common event often triggered by a cold beverage and that it was not life-threatening. Patient education by the clinical staff reinforced the necessity of avoiding cold liquids or foods for several days after receiving oxaliplatin. After four cycles of therapy, the patient presented with mild peripheral neuropathy and an elevation in ALT of 122. The most likely cause of the elevation was thought to be the oxaliplatin, but the clinicians also considered whether the increased level of ALT signified progression of disease in the liver. In addition, Mrs K was questioned about the use of herbal medications and other supplements. She admitted using several alternative medicines and was asked to discontinue them. The decision was made to stop oxaliplatin, continue with 5-FU/LV and bevacizumab, and monitor the patient s liver enzymes. Two weeks later her ALT level was 85, and was returned to normal in 4 weeks. The regimen of FOLFOX plus bevacizumab was then resumed. Restaging scans showed a 50% decrease in her liver lesion, but the lesion was still considered unresectable. Mrs K was encouraged by the scan results, and chemotherapy continued. A neuropathy assessment was performed before each dose of oxaliplatin was given. Until about the ninth cycle, the patient had experienced only minimal peripheral neuropathy for a few days after each dose of oxaliplatin. Grade 3 thrombocytopenia was noted after cycle 9, and the oxaliplatin dose was reduced. Before cycle 12, Mrs K reported having great difficulty buttoning her clothing and a lack of sensation on the bottoms of her feet, which represents grade 3 neuropathy. With these symptoms of neuropathy now more persistent and interfering with the patient s activities of daily living, oxaliplatin was discontinued. Four months later, the liver lesion remained stable and therapy with 5-FU/LV plus bevacizumab continued. Mrs K s neuropathy was downgraded to grade 1 and, at that point, her clinicians were considering the resumption of oxaliplatin. Discussion Many options are now available for the treatment of mcrc. 4 Mrs K was given a thorough explanation of several chemotherapy regimens, including information on efficacy and possible toxicities. 5 Mrs K s decision to receive FOLFOX plus bevacizumab was based in part on the regimen s toxicity profile and her family encouragement and support. Although she responded well to FOLFOX plus bevacizumab, her solitary liver lesion remained unresectable. Her oncology team performed neuropathy assessments before each dose of oxaliplatin. Persistent neuropathy precluded Mrs K from receiving further oxaliplatin. Given that her neuropathy was minimal and the liver lesion did not progress while she received oxaliplatin, the option remained open for her to resume oxaliplatin dosing at some point in the course of therapy. Summary of Key Points Elevation of liver enzymes is a known toxicity of oxaliplatin. Patient education should be emphasized throughout therapy. Approximately 30% of all CRCs do not produce abnormally high levels of CEA. Thorough assessment of neuropathy should occur before each dose of oxaliplatin given. Dose reductions may be necessary for thrombocytopenia and are required when thrombocytopenia is greater than grade 2. For a majority of patients, chronic neuropathy caused by oxaliplatin resolves or decreases in intensity over a period of many months once the drug is discontinued. CASE STUDY #3: CONSIDERATIONS FOR THERAPY: XELOX WITH BEVACIZUMAB VERSUS FOLFIRI/FOLFOX WITH BEVACIZUMAB While traveling to Hawaii for a vacation, Ms W, 48 years old and newly divorced, experienced sharp and cramping abdominal pain along with bright red blood per rectum. She sought medical attention and after evaluation was admitted to the hospital. An emergent colonoscopy found a partially obstructive, 5-cm lesion in her descending colon and a CT scan revealed

5 40 LASSERE ET AL two lesions in her liver. The rest of her metastatic workup was negative. Her baseline preoperative CEA level was 35.6 ng/ml. Therapy options were discussed, and the ultimate decision was to return home for a colectomy followed by neoadjuvant chemotherapy plus bevacizumab in hope that her liver lesions would become resectable. Findings included: Past medical history: mild hypertension, depression, mild peripheral vascular disease Past surgical history: hysterectomy because of uterine bleeding in 2001 Family history: mother diagnosed with stage I colon cancer at age 62, alive and well; father died of a myocardial infarction at age 71 Social history: divorced, no children, minimal family and social support in the home Current medications: sertraline, 75 mg daily; lisinopril, 10 mg daily; aspirin, 325 mg daily No known drug, food, or environmental allergies Current laboratory values: all WNL ECOG performance status: 1 Treatment Options and Interventions After surgery, chemotherapy options suggested to Ms W included bevacizumab plus either FOLFIRI or FOLFOX. The patient was adamant about not having a long-term venous access catheter placed and opted to receive the oral fluoropyrimidine capecitabine with oxaliplatin (the combination regimen XELOX) daily for 2 weeks plus infusional bevacizumab, even though she was informed that data were not yet available regarding the efficacy of XELOX in combination with bevacizumab. Patient education focused on potential toxicities of therapy, including oxaliplatin-associated neurotoxicity, hand-foot syndrome (HFS), neutropenia, the possibility of nosebleeds or other bleeding, and the need to monitor her hypertension. Ms W s nurse stressed the importance of taking all of her oral capecitabine and providing timely communication to the treatment team about any side effects to reduce the potential for drug toxicity. After two cycles of XELOX, the patient returned to the office for evaluation. Assessment focused on manifestations of HFS and peripheral neurotoxicity. She reported mild and short-lived cold sensory symptoms and mild redness and tenderness of her hands. She stated her feet were fine and declined to remove her shoes. After the nurse noted the patient s gait showed a small hesitation while walking, she again asked the patient to remove her shoes and found Ms W had grade 2 HFS of her feet. In further conversation about this the patient became tearful, stating she was afraid to report her symptoms because her therapy might be changed. Further discussion of side effects and efficacy relieved some of the patient s anxiety about treatment. Capecitabine was held until symptoms of HFS resolved (to grade 0) and then was resumed at 100% of her original dose. After 3 months of chemotherapy, a repeat staging CT scan showed that one liver lesion had disappeared completely and the other could now be considered resectable. Her CEA level was 7.5. The remaining liver lesion was successfully removed, and after surgery the patient s CEA dropped to 3.0 ng/ml. At the time of this writing, Ms W was completing her planned treatment with XELOX plus bevacizumab for a total of 6 months of therapy. A subsequent increase in HFS symptoms after cycle 9 prompted a reduction of capecitabine to 75% of the original dose. She continued to tolerate this dose without worsening of HFS symptoms and was to be followed with surveillance visits, serial CEA measurements, and periodic scans to assess for recurrent disease. Discussion There have been exciting advances in the treatment of mcrc, and with five new agents approved in the treatment of this common disease, initial choices in therapy may be influenced by patient desires as well as considerations of treatment efficacy. Ms W was very hesitant to have an implanted device placed for the infusion of continuous 5-FU therapy. Therefore, substituting an oral fluoropyrimidine is a rational choice for this patient. The combination of capecitabine with oxaliplatin was studied in 96 patients and found to be an effective first-line therapy for mcrc, as well as a more convenient regimen. 6,7 The addition of bevacizumab to XELOX is currently under study, and initial data reported at the 2006 annual meeting of the American Society of Clinical Oncology (Atlanta, GA) have been promising. 8 Offering the combination to this patient met her needs for primarily oral therapy. Current research has shown that the combination is potentially efficacious for this disease.

6 CASE STUDIES IN METASTATIC COLORECTAL CANCER 41 Summary of Key Points All protocol options must be discussed with patients and their understanding of the information should be evaluated. Reported efficacy of potential regimens should be explained as well as the method of drug administration. If the patient opts for an alternative therapy, the plan should be thoroughly discussed. The potential substitution of oral capecitabine for infusional 5-FU has been shown to be a reasonable option, but larger studies are needed to confirm the equivalence of XELOX to FOLFOX. 9 A current trial is recruiting patients to answer this question, but for the time being patients should know that there may be possible differences in efficacy when they choose oral capecitabine over intravenous fluoropyrimidines. If primary oral therapy is chosen, adherence to the regimen must be stressed and assessed if possible (ie, by having the patient bring in the capecitabine bottle for a pill count). Patients must verbalize their understanding of key toxicities as well as self-care strategies and conditions they should be reporting. Nurses and clinicians must be vigilant in patient assessment, particularly with regard to physical symptoms not readily apparent. pain, anorexia, and obstipation for the past 5 days. Findings included: Past medical history: hyperlipidemia, hypertension, and hypothyroidism Past surgical history: none before colon resection Family history: mother died at age 54 of breast cancer, father died at 90 of cardiac disease Social history: patient is divorced and lives alone in an apartment. He has two children who live nearby and help him get to appointments and who are becoming more involved in his care. He is as yet unwilling to accept his daughter s invitation to live with her because he values his independence. Current medications: losartin, 50 mg daily; lovastatin, 40 mg daily; levothyroxin, 0.75 mg daily; pantoprazole, 40 mg twice daily; lactulose, 30 cc twice daily; morphine, 15 mg every 4 hours; and senna at night and docusate 3 times daily Allergies: oxycodone (caused vomiting); oxaliplatin (induced shaking, chills, and severe back pain) Current laboratory values: electrolytes, WNL (sodium, 134; potassium, 5.0; chloride, 104; and carbon dioxide, 17); creatinine, 1.6 ECOG performance status: 2 CASE STUDY #4: PATIENT UNDERGOING THERAPY FOR MCRC: CETUXIMAB, BEVACIZUMAB, AND IRINOTECAN Mr J, age 56, was initially diagnosed with colon cancer by colonoscopy in November 2004 and underwent surgery to remove the bulk of the tumor. He was treated with six cycles of FOLFOX plus bevacizumab, and in July 2005 he was told he was cancer-free. However, at his 3-month follow-up, a positron-emission tomography (PET)/ CT scan confirmed tumor recurrence, this time in the stomach. The patient was treated with FOLFIRI for 6 months when a CT scan showed progression to the liver. A PET scan demonstrated extensive liver disease (multiple liver lesions, a mass in the porta hepatis, left portal vein occlusion, and biliary ductal dilatation), peritoneal carcinomatosis, ascites, and numerous suspicious pulmonary nodules. At this point Mr J also reported a 6-week history of left-sided abdominal Treatment Options and Interventions In considering therapeutic options for Mr J it was noted he had already received oxaliplatin, which led to severe back pain, so this agent was not considered again. His performance status was worsening, but he felt his quality of life was good enough to try another round of different chemotherapy and his children were supportive of his decision. Therapy was changed to cetuximab (Erbitux; ImClone Systems Inc and Bristol Myers Squibb Co, New York, NY), bevacizumab, and irinotecan (CBI). 10 There were several factors to consider in planning treatment and monitoring for Mr J. His BP before starting therapy was 136/74. Because his treatment regimen was to include bevacizumab, the presence of comorbid hypertension would require frequent monitoring. He was already testing his urine for protein by dipstick, which had thus far been negative; but the decision was made that the nursing staff would collect a 24-hour urine specimen for the detection of protein and would

7 42 LASSERE ET AL closely follow the patient during treatment with bevacizumab. Mr J previously received irinotecan without experiencing diarrhea and became somewhat constipated from the morphine. Close monitoring during cetuximab infusions was also indicated because his reaction to oxaliplatin could potentially increase his susceptibility to cetuximab reactions. 11 He had no history of skin diseases, but the nursing staff was to monitor him closely for skin rash along with his electrolytes, creatinine, and fluid balance. The patient had a dual-lumen implanted port in place for therapy. Mr J received his initial cycle of CBI as an inpatient after his obstipation was relieved. He was premedicated with 50 mg of diphenhydramine and 650 mg of acetaminophen, tolerated all three agents in the CBI regimen well and without evidence of hypersensitivity, and was discharged home. Mr J is to be evaluated for tumor response by PET/CT after two cycles of CBI. If he has further progression at that time, a palliative care consult will be initiated to explore possible admission to hospice. Discussion All members of the health care team, along with the patient and his children, discussed current options, including best supportive/palliative care and entering a limited clinical trial to evaluate possible benefits of CBI therapy. His children were supportive of his decision to pursue therapy and available to ensure close follow-up, particularly because of his relative debilitation and risks for fluid, electrolyte problems, and drug toxicities (eg, rash, increased BP, and positive urine protein). Mr J was to be seen weekly to determine if he was feeling better and whether his performance status was improving and to closely follow any symptoms. He was to continue CBI as long as it enhanced his functioning and quality of life. Summary of Key Points All avenues of therapy have been discussed. Patient is nearing end of continuum; if this fails, best supportive care would be an option. Laboratory data need to be monitored closely as this patient is already debilitated and at significant risk of toxicity. Both the patient and his family are aware of the patient s current disease status and prognosis. Close monitoring is needed to ensure that the patient will not experience significant toxicity from therapy and have his quality of life worsened or survival cut short. CONCLUSION In summary, we have presented four typical cases with the diagnosis of mcrc. The authors have described significant toxicities that patients commonly experience and then have discussed appropriate anticipatory management and interventions for each toxicity. It is incumbent on all practicing oncology nurses to be aware of the side-effect profile of the therapeutic agents used in each case. We hope these examples will be useful in aiding oncology nurses to better deal with these common toxicities in practice. Patients who have CRC look to their oncology nurses to be mentors and guides along the treatment continuum, to aid them in self-care management and problem-solving to optimize their quality of life and potentially extend life. REFERENCES 1. Benson A, Ajain A, Catalano R, et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 2004;22: Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX 6 or the reverse sequence in advanced colorectal cancer: A randomized GERCOR study. J Clin Oncol 2004;22: Eloxatin prescribing information. Bridgewater, NJ: Sanofi-Aventis; April Available at: (accessed July 9, 2006). 4. Wilkes G. Therapeutic options in the management of colon cancer: 2005 update. J Clin Oncol 2005;9: Yamamoto D, Viale P, Roessner K, et al. The clinical use of tumor markers in select cancers: Are you confident enough to discuss them with your patients? Oncol Nurs Forum 2005;32: Borner MM, Dietrich D, Stupp R, et al. Phase II study of capecitabine and oxaliplatin in first- and second-line treatment of advanced or metastatic colorectal cancer. J Clin Oncol 2002;20: Cassidy J, Tabernero J, Twelves C, et al. XELOX (capecitabine plus oxaliplatin): Active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 2004;22:

8 CASE STUDIES IN METASTATIC COLORECTAL CANCER Berry SR, Cunningham D, Michael M, et al. Preliminary safety of bevacizumab with first-line Folfox, Capox, Folfiri and capecitabine for mcrc First B.E.A.Trial [abstr 3534]. Proc Am Soc Clin Oncol 2006;24:154s. 9. Kopetz S, Hoff PM. Cytotoxic chemotherapy for advanced colorectal cancer. Recent advances in management. Oncology 2005;19(suppl 6): Saltz LB, Lenz H, Hochster H, et al. Randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer [abstr 3508]. Proc Am Soc Clin Oncol 2005;23:348s. 11. Cunningham D, Humblet Y, Sienna S, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecanrefractory metastatic colorectal cancer. N Engl J Med 2004; 351: