XELOX in Elderly Patients with Metastatic Colorectal Cancer
Abstract & Commentary
William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.
Synopsis: Elderly patients with metastatic colon cancer were treated with capecitabine and oxaliplatin in the XELOX regimen. Response rate, progression-free survival, and overall survival were not significantly different than published reports of this active regimen in younger cohorts; and there was generally a low level of hematotoxicity, neurotoxicity, and hand-foot syndrome. Thus, the combination represents an appropriate treatment option for selected elderly patients with this disease.
Source: Comella P, et al. Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma. Cancer. 2005;104:282-289.
Capecitabine has been shown to be at least equivalent and perhaps more effective than bolus 5-fluorouracil/leucovorin (5-FU/LV) for the treatment of metastatic colorectal cancer (MCC). By virtue of its oral formulation it is particularly well-suited for older patients. The current trial from the Southern Italy Cooperative Oncology Group examined the substitution of capecitabine for 5-FU/LV in the FOFLOX4 regimen. In the new regimen oxaliplatin (85 mg/m2) was administered on Day 1 and capecitabine (1000 mg/m2) on Days 2-15 (XELOX regimen) of each 21-day cycle. In the absence of Grade > 2 hematological toxicity, oxaliplatin was increased to 100 mg/m2 in the second cycle, and in the absence of Grade > 2 nonhematological events during Cycle 2, capecitabine was increased to 1250 mg/m2 twice daily for the third and subsequent cycles. After analysis of the first 35 patients, subsequent patients did not have capecitabine escalation in cycle 3 but oxaliplatin dose was increased to 110 mg/m2 in cycle 2 and to 130 mg/m2 in cycle 3.
The median age of the 76 patients enrolled was 75 years. There were 2 complete responses and 29 partial responses for an overall response rate (RR) of 41%. The median progression-free survival (PFS) was 8.5 months and the median overall survival (OS) was 14.4 months. In a multivariate analysis, the presence of disease symptoms affected both PFS and OS, whereas OS also was independently affected by male gender and disease spread. Age had no independent effect on PFS or OS. Grade > 3 hematological toxicity occurred in 5%, Grade > 3 neurotoxicity in 8%, and severe hand-foot syndrome in 13% of patients.
COMMENTARY
Colorectal cancer is the third most common cause of cancer-related death in the elderly,1 and 90% of cases are diagnosed in people older than 50 years of age.2 Interestingly, as with breast cancer, the number of deaths from colorectal cancer has been declining an average of 1.8% per year during the past 15 years, possibly as a result of the success of screening and polyp removal.3 Yet, the elderly continue to sustain the greatest burden with 78% of all colon cancer deaths occurring at 65 years or older.1
5-FU has been the backbone of most treatment regimens for metastatic colorectal cancer, now most commonly in combination with leucovorin, irinotecan, oxaliplatin, or bevacizumab.4,5 5-FU, developed one-half century ago, was the first chemotherapeutic agent used for solid tumor patients. Numerous doses, routes of administration and schedules have been explored for various tumor types. Administration by continuous infusion has been shown to be particularly effective for breast and colorectal cancers, but mucositis and marrow depression was shown to increase risk of infection and thrombosis.6 An alternative to infusional 5-FU is oral capecitabine, a tumor-activated fluoropyrimidine,7 approved by the FDA for treating metastatic breast cancer either alone or in combination with docetaxel, as a single agent for the treatment of MCC, and, most recently, for the adjuvant treatment of Duke’s stage C colon cancer.
In the current clinical trial of elderly patients with MCC who were estimated to have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) scale, a 41% response rate was achieved when receiving XELOX as first-line treatment. The investigators estimated that approximately 75% achieved disease control and this translated into a median PFS of 8.5 months and a median OS of 14.4 months. These findings are comparable to other reports of the XELOX regimen examined in younger colorectal cancer cohorts.8 The regimen was found to be generally well tolerated, and Grade 3 or higher toxicity was infrequent. Perhaps the most important contribution from this investigation is the demonstration of appropriate dose levels. Capecitabine and oxaliplatin do not have overlapping toxicities and the tolerability of the combination was quite satisfactory, particularly at a capecitabine dose of 1000 mg/m2.
References
1. National Institute on Aging, National Cancer Institute. Exploring the role of cancer centers for integrating aging and cancer research. Available online at: www2.nia.nih.gov/health/nianci/
2. American Cancer Society. Cancer facts and figures 2005. Available at: www.cancer.org/downloads/STT/CAFF2005f4PWSecured.pdf.
3. American Cancer Society. Cancer facts and figures 2004. Available at: http://www.cancer.org/docroot/STT/stt_0_2004.asp?sitearea=STT&level=1
4. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: colon cancer. Version 1.2005. Available online at: www.nccn.org/professionals/physician_gls/PDF/colon.pdf.
5. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: rectal cancer. Version 4.2005. Available online at: www.nccn.org/professionals/physician_gls/PDF/rectal.pdf.
6. Twelves C, et al. Capecitabine (Xeloda) improves medical resource use compared with 5-fluorouracil plus leucovorin in a phase III trial conducted in patients with advanced colorectal carcinoma. Eur J Cancer. 2001;37:597-604.
7. Schuller J, et al. Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients. Cancer Chemother Pharmacol. 2000;45:291-297.
8. Cassidy J, et al. XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol. 2004;22: 2084-2091.
Elderly patients with metastatic colon cancer were treated with capecitabine and oxaliplatin in the XELOX regimen. Response rate, progression-free survival, and overall survival were not significantly different than published reports of this active regimen in younger cohorts; and there was generally a low level of hematotoxicity, neurotoxicity, and hand-foot syndrome. Thus, the combination represents an appropriate treatment option for selected elderly patients with this disease.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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