Current status of capecitabine in the treatment of colorectal cancer

Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to fluorouracil (5-FU) within cancer cells. Data from two large phase III trials performed in patients receiving first-line chemotherapy for metastatic colorectal cancer showed that capecitabine yielded higher objective response rates and equivalent median time to tumor progression and overall survival rates as 5-FU/leucovorin. In these studies, capecitabine demonstrated lower rates of diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin, but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural extension of this work has been to evaluate substitution of capecitabine for 5-FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin). This is especially important due to concerns regarding toxicities observed with regimens that combine bolus 5-FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase H trials of capecitabine in combination with irinotecan or oxaliplatin in patients with advanced disease indicate that the combinations are well tolerated and produce response rates that are in the range of those that would be expected with infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III trials have been initiated in the advanced disease and adjuvant settings and should help determine the efficacy, toxicity, and tolerability of the capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.