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Reduced-Dose Capecitabine May Be Reasonable Alternative to Combination Chemotherapy

Reduced-Dose Capecitabine May Be Reasonable Alternative to Combination Chemotherapy

OTTAWA, CANADA-For older and less fit cancer patients, who are more likely to experience greater toxicity but less benefit from combination chemotherapy, a more reasonable alternative might be single-agent and reduced-dose chemotherapy. That was the rationale behind a Canadian phase I/II trial to assess reduced-dose capecitabine (Xeloda) as part of a sequential single-agent therapy for older and less fit patients with advanced colorectal cancer (abstract 3577). The data were presented by M. C. Cripps, MD, of the Ottawa Regional Cancer Center. Results showed an overall median survival of 14.8 months and a "respectable 19.7 month median survival in older patients" with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, the investigators reported. This finding "suggests sequential single-agent therapy beginning with capecitabine may be a reasonable and well-tolerated alternative to combination chemotherapy," the investigators concluded. Five Overlapping Subgroups The multicenter trial was designed to test reduced-dose capecitabine in a population of adults with advanced colorectal cancer "clearly shown not to derive survival benefit from combination chemotherapy." Study participants could have undergone no prior chemotherapy for metastatic disease, and adjuvant fluorouracil therapy must have been completed 6 or more months before study enrollment. The male/female ratio for the 221 patients accrued was 142/79, or 64%/ 36%. Patients fell into one or more of the following five subgroups at baseline:

  • Age ≥ 65 years (173 patients [78%])
  • ECOG PS ≥ 1 (145 patients [66%])
  • Liver enzyme abnormalities (5 patients [2%]).
  • Prior pelvic radiation therapy (54 patients [24%])
  • Liver enzyme abnormalities (5 patients [2%]).
The number of patients with abnormal liver function tests was considered insufficient to move this subgroup into the phase II stage to evaluate for toxicity. Capecitabine was administered at 1,000 mg/m2 twice daily on days 1 to 14 every 21 days. The median number of cycles was five. Prior pelvic radiation therapy required dose reduction to 750 mg/m2 twice daily due to diarrhea in the third cycle. Factors Predicting Survival Among the 191 evaluable patients, the overall response rate (complete plus partial responses) was 19%, and the disease control rate (overall response plus stable disease) was 81%. Disease control rates were somewhat lower for those patients with poorer ECOG PS, an elevated LDH level, and higher doses of pelvic radiation therapy (see Table 1). The median disease progressionfree survival was 5.2 months (95% confidence interval [CI], 4.5-6.9). The overall median survival at the time of this report was 14.8 months (95% CI, 11.8-17.0). At median follow-up of 11.1 months, 82 patients were still alive. Factors predicting shorter survival were poor ECOG PS and elevated LDH level. Although the median survival time for patients with an ECOG PS of 0 was 19.7 months, it fell to 13.2 months for patients with an ECOG PS of 1 and 6.8 months for patients with an ECOG PS of 2. Grade 3/4 Adverse Events Of the 213 patients evaluable for toxicity, 23 had grade 3/4 adverse events. The two most common adverse events were hand-foot syn drome, experienced by eight patients, and diarrhea, experienced by seven. Other Canadian institutions participating in the trial were the London Regional Cancer Centre, British Columbia Community Oncology Associates in Vancouver, the British Columbia Cancer Agency in Kelowna, the Windsor Regional Cancer Centre, the Kingston Regional Cancer Centre, and the Grand River Regional Cancer Centre in Kitchener.
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