The combination of capecitabine and oxaliplatin in metastatic colorectal cancer.

Abstract

Introduction Two randomized phase III studies were conducted in France comparing the combination of 5-fluorouracil (5-FU)/leucovorin (LV) regimen with or without oxaliplatin as first-line treatment for patients with metastatic colorectal cancer.1,2 Although each study employed a different schedule of administration of 5-FU/LV, both studies showed that the combination of 5-FU/LV plus oxaliplatin (FOLFOX regimen) resulted in a significantly improved overall response rate (RR; 53% vs. 16%1; P < 0.001 and 51% vs. 22%2; P = 0.0001) and median time to disease progression (8.7 months vs. 6.1 months1; P = 0.048 and 9.0 months vs. 6.2 months2; P = 0.0003) compared with patients treated with 5-FU/LV alone. In these studies, the overall survival was not significantly prolonged with the addition of oxaliplatin to 5-FU/LV. • Daily oral dosing with capecitabine results in sustained intracellular exposure to 5-FU that mimics continuous intravenous (I.V.) infusion of 5-FU. 3 The combined results of 2 large phase III studies in 1207 metastatic colorectal cancer patients comparing oral capecitabine with 5-FU/LV as first-line therapy showed that treatment with capecitabine led to a better overall RR (26% vs. 17%; P < 0.0002) compared with treatment with 5-FU/LV. 4 Furthermore, treatment with capecitabine also resulted in an improved toxicity profile, with the incidence of gastrointestinal toxicity (diarrhea, nausea, and stomatitis) significantly reduced (P < 0.001) compared with treatment with 5-FU/LV. oxaliplatin in place of 5-FU/LV. Further rationale for combining oxaliplatin with capecitabine includes preclinical evidence of synergistic activity of oxaliplatin with fluoropyrimidines as well as their single-agent efficacies in colorectal cancer, easier administration, and good safety profile.5