BERN, Switzerland-A study of capecitabine(Drug information on capecitabine) (Xeloda) and two different schedules of administration of irinotecan(Drug information on irinotecan) (CPT-11, Camptosar) as first-line therapy for patients with metastatic colorectal cancer found that a 3-week schedule achieved better response than a 1-week schedule, with reduced toxicity. The results were reported by Markus Borner, MD, associate professor, Institute of Medical Oncology, Inselspital, Bern, Switzerland (ASCO abstract 1068). Adding irinotecan to fluoropyrimidines is a new standard in the treatment of metastatic colorectal cancer. According to Dr. Borner, "Well tolerated combination regimens have used irinotecan in combination with infusional fluorouracil(Drug information on fluorouracil) (5-FU) plus leucovorin. Oral capecitabine might be more convenient than infusional fluorouracil. Furthermore, preliminary study results suggest that the combination of capecitabine and irinotecan is feasible. However, irinotecan can be administered in different schedules and it is not clear which schedule is the most advantageous in combination with capecitabine." Objectives and End Point The primary objective of the study was to compare the efficacy of different irinotecan schedules in combination with capecitabine in chemotherapy-naive metastatic colorectal cancer patients. The main end point of this study was the objective tumor response rate. The secondary objectives were to assess toxicity, time to treatment failure, time to progression, and overall survival associated with the two different schedules. "We performed an exploratory phase II study comparing weekly irinotecan to 3-weekly irinotecan in combination with capecitabine," Dr. Borner explained (Table 1). In treatment arm A, irinotecan was administered every week at a dose of 70 mg/m2 on days 1, 8, 15, 22, and 29. In treatment arm B, irinotecan was given every 3 weeks at a dose of 300/240 mg/m2 on day 1 and day 22. Both arms received capecitabine 1,000 mg/m2 twice daily on days 1 to 14 and days 22 to 35 every 42 days. Because of newly available phase I toxicity data, the irinotecan dose in treatment arm B was reduced from 300 to 240 mg/m2 after January 4, 2002. To be eligible for the study, patients must have: nonresectable advanced or metastatic colorectal cancer, no prior chemotherapy for advanced or metastatic cancer, good performance status (World Health Organization 0/1), and measurable disease. The two arms were well balanced. Response and Toxicities The objective response rates as assessed by investigators were 29% for arm A, and 43% for arm B. Median time to progression was 6.9 months for arm A, and 9.3 months for arm B. The median overall survival was 14.7 months in arm A and not reached yet in arm B. The most important toxicities were grade 3/4 diarrhea (32% in arm A vs 19% in arm B) and grade 2/3 alopecia (21% vs 65%). Other grade 3/4 toxicities were rare (less than 5%). In summarizing the results of the study, Dr. Borner said, "The combination of irinotecan plus capecitabine is active in the treatment of first-line metastatic colorectal cancer. Considering the favorable toxicity, time to progression, and patient convenience, in addition to the main study end point of objective tumor response rate, the every-3-week schedule of capecitabine plus irinotecan will be used for further comparative studies."