Abstract
Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150mg/m(2). Median follow-up in a subsequent Phase II study using this dose was 28months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16months and median overall survival (OS) was 28months. Median PFS was longer for patients with an early treatment response (28 vs. 9months for others; P=0.024), or early tumor shrinkage (25 vs. 9months for others; P=0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9months for others; P=0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22months for others; P=0.006) or surgery (median not reached vs. 22months for others, P=0.002). K-ras mutations status did not influence PFS (P=0.88) or OS (P=0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity.