GLASGOW, Scotland—"Development of capecitabine(Drug information on capecitabine) (Xeloda) was inspired by the fact that what is wanted is an oral tablet that will mimic infusional fluorouracil(Drug information on fluorouracil) (5-FU) and will have tumor-selective activation. Clearly, about 90% of patients prefer oral therapy, but they do not want to sacrifice efficacy for convenience," Christopher Twelves, MD, stated. A number of recent clinical trials suggest that capecitabine might be a simpler substitute for 5-FU in colorectal cancer regimens and Dr. Twelves, a consultant in medical oncology at Cancer Research UK, Glasgow, Scotland, discussed this possibility at the First International Colorectal Cancer Congress in Palm Beach, Florida.
A phase III study compared single-agent capecitabine to the Mayo Clinic bolus 5-FU-based regimen in patients with metastatic colorectal cancer. Capecitabine was given at 1,255 mg/m2 bid for 2 weeks on and 1 week off. The trial was powered to demonstrate equivalence, meaning that capecitabine was not any worse than standard therapy. The overall response rate (complete and partial response) was 26% with capecitabine vs 17% with 5-FU/leucovorin (P < .0002). "Response was also achieved earlier with capecitabine," Dr. Twelves said.
Toxicity analysis showed that 5-FU/leucovorin caused more stomatitis, and capecitabine caused more hand-foot syndrome (HFS). However, capecitabine was associated with a much lower need for hospitalization. The number of hospitalizations was 40 with capecitabine vs 49 with 5-FU/leucovorin (a decrease of 18.4%). The number of patients requiring hospitalization was 35/297 with capecitabine vs 47/295 with 5-FU/leucovorin, a decrease of 25.5%.
Capecitabine has been approved for first-line treatment of metastatic disease. Dr. Twelves said that it has high efficacy, superior response rate, improved overall survival, is better tolerated than previous regimens, and yields cost savings.
Combined With Oxaliplatin(Drug information on oxaliplatin)
Investigators next began to ask whether capecitabine might completely replace 5-FU in the treatment of colorectal cancer and whether capecitabine might be combined with oxaliplatin (Eloxatin), because each agent is active in this setting and there is no overlap in toxicities.
A capecitabine/oxaliplatin combination was tried as first-line treatment for metastatic colorectal cancer in a nonrandomized multicenter phase II trial of 96 patients. Overall response rate was 55% (95% CI 46%-95%). "There was a consistent response rate above 50% in all patient subgroups, including those with prior adjuvant chemotherapy and those with liver or lung metastases," Dr. Twelves said.
