XELOX: Safe and Effective for Elderly Patients with Colon Cancer
Abstract & Commentary
By William B. Ershler, MD, Editor, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.
Synopsis: A phase II study of combined capecitabine and oxaliplatin for elderly patients with metastatic colorectal cancer demonstrates safety and efficacy. The regimen may well become the treatment of choice in this setting because of the added convenience of oral administration of capecitabine.
Source: Feliu J, et al. XELOX (capecitabine plus oxaliplatin) as first-line treatment for elderly patients over 70 years of age with advanced colorectal cancer. Br J Cancer. 2006;94:969-975.
Colorectal cancer is primarily a disease of older people, with more than 50% of patients being older than age 70.1 Although chemotherapy has demonstrated benefit for colorectal cancer patients, older patients are less likely to receive treatment, either in the adjuvant2,3 or metastatic4 setting. The purpose of the current study was to examine the efficacy and tolerability of combined capecitabine and oxaliplatin (XELOX) in elderly patients who present with metastatic disease. The premise for the study is that this combination might be equally efficacious, but better tolerated and more convenient than comparable regimens that include parenteral fluorouracil (FU), leucovorin (LV), and irinotecan.
Fifty elderly (> 70 years) patients with metastatic colorectal cancer (MCRC) were enrolled in this phase II patients. Each received oxaliplatin 130 mg/m2 on day 1 followed by oral capecitabine 1000 mg/m2 twice daily on days 1-14 every three weeks. Patients with creatinine clearance of 30-50 mL/min received a reduced dose of capecitabine (750 mg/m2) twice daily on the same schedule. By intent-to-treat analysis, the overall response rate was 36% (95% CI, 28-49%), with 3 (6%) complete and 15 (30%) partial responses. In total, 18 patients (36%) had stable disease and 14 (28%) progressed. The median times to disease progression and overall survival were 5.8 months and 13.2 months, respectively.
In general, the regimen was well tolerated. Nonetheless, 32 patients (64%) had an adverse event, but usually grade 1 or 2. The main adverse events were gastrointestinal and hematological. A total of 14 patients (28%) had grade 3/4 adverse events: 11 (22%) diarrhea, 8 (16%) asthenia, 7 (14%) nausea/vomiting, and only 2 (4%) with hand/foot syndrome and 1 (2%) with neurotoxicity.
Thus, the authors conclude that XELOX is well tolerated and effective therapy for elderly patients with MCRC. Furthermore, they speculate that the added convenience of oral treatment may be particularly agreeable to elderly patients who might have less favorable venous access and possibly transportation issues to and from clinic.
Commentary
Capecitabine, either alone or in combination has proven to be a safe and effective drug for elderly patients with either colorectectal or breast cancer.5 Capecitabine monotherapy as a first-line therapy for metastatic colorectal cancer has been shown to be more active in elderly patients than standard 5-FU/LV therapy. In a randomized, controlled study comparing single-agent oral capecitabine with the Mayo Clinic regimen (bolus 5-FU/LV) in patients > 60 years of age,6 the overall response rate (ORR) was significantly greater with capecitabine (26% vs 16%; P = 0.018). As well, the ORR among patients treated with single-agent capecitabine did not significantly differ between those > 60 years of age and those ≤ 60 years of age (26% vs 24%; P = 0.688). Similarly, there was no significant difference in response rates in patients ≥ 65 years of age and < 65 years of age treated with XELOX (52% vs 58%; P = 0.54).7 These findings suggest that elderly patients with colorectal cancer who are treated with capecitabine are as likely to respond favorably to therapy as younger patients. Thus, the current Phase II study, focused particularly on elderly patients, confirmed suspicions that the combination would be effective. In fact the response rate of 36% and median time to progression (5.8 months) are quite similar to other published reports of XELOX treatment8-10 although the median survival was somewhat less (13.2 months compared with 17-20 months in the other studies.8-10 However, the current study was performed exclusively on elderly patients and the survival was comparable to other regimens so designed.11,12
There was, however, one surprising finding in the current report with regard to toxicity. Overall, the combination appeared comparable to other treatment regimens in this regard. Noteworthy, however was the very low incidence of grade 3/4 neurotoxicity which was less than one might expect, given the dose of oxaliplatin and the age of the patients. Indeed, in the Cassidy report,10 grade 3/4 neurotoxicity occurred in 17%. Although the explanation for this is not obvious, the authors speculate that in the current series the cumulative dose of oxaliplatin was less (median, 4.5 doses per patient compared with 8 doses in the Cassidy trial), suggesting that with continued treatment may be associated with increased rates of developing this adverse outcome.
Thus, the current report confirms the confirms the efficacy and safety in the elderly of the XELOX regimen, when compared to other commonly used combinations for metastatic colorectal cancer. The combination has definite advantages when it comes to convenience, particularly for elderly patients.
References
1. Edwards BK, et al. Annual report to the nation on the status of cancer, 1973-1999, featuring implications of age and aging on U.S. cancer burden. Cancer. 2002;94:2766-2792.
2. Potosky A, et al. Age, sex, and racial differences in the use of standard adjuvant therapy for colorectal cancer. J Clin Oncol. 2002;20:1192-1202.
3. Sargent DJ, et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med. 2001;345:1091-1097.
4. Wasil T, Lichtman SM. Treatment of elderly cancer patients with chemotherapy. Cancer Invest. 2005;23:537-547.
5. Ershler WB. Capecitabine use in geriatric oncology: An analysis of current safety, efficacy, and quality of life data. Crit Rev Oncol Hematol. 2006;58:68-78.
6. Hoff PM, et al. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001;19:2282-2292.
7. 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.
8. Borner MM, 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;20:1759-1766.
9. Zeuli M, et al. Phase II study of capecitabine and oxaliplatin as first-line treatment in advanced colorectal cancer. Ann Oncol. 2003;14:1378-1382.
10. 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.
11. Aparicio T, et al. Oxaliplatin- or irinotecan-based chemotherapy for metastatic colorectal cancer in the elderly. Br J Cancer. 2003;89:1439-1444.
12. Comella P, et al. Capecitabine plus oxaliplatin for the first-line treatment of elderly patients with metastatic colorectal carcinoma: final results of the Southern Italy Cooperative Oncology Group Trial 0108. Cancer. 2005;104:282-289.
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