Multinational Trial Supports Use of Capecitabine Plus Oxaliplatin for Metastatic Colorectal Cancer

CHICAGO-As first-line treatment for metastatic colorectal cancer, XELOX, the combination of oral capecitabine(Drug information on capecitabine) (Xeloda) plus oxaliplatin(Drug information on oxaliplatin) (Eloxatin), is safe and effective. These mature results of a multinational trial (ASCO abstract 1023) were reported by Professor Eric Van Cutsem, MD, PhD, senior academic staff member at University Hospital- Gasthuisberg, Leuven, Belgium. Dr. Van Cutsem noted that a significant feature of capecitabine is the substantially improved convenience that it offers compared with infusional 5-FU. XELOX requires only one clinic visit every 3 weeks, simplifying therapy and allowing the patient to lead a more normal lifestyle. According to Dr. Van Cutsem, "tumor- activated capecitabine was designed to mimic infused 5-FU, and with advantages in convenience and patient preference, capecitabine should also replace 5-FU/leucovorin in combination." High Response Rates Patients in the phase II trial received a 2-hour infusion of oxaliplatin 130 mg/m² on day 1, and oral capecitabine 1,000 mg/m² bid on days 1 to 15, followed by 7 days off. The treatment continued for 11 cycles in patients with tumor response or stable disease, and the median number of cycles was 9. After a minimum follow-up of 24 months, XELOX achieved an overall response rate of 55%. "The high response rate was maintained, with all subgroups achieving a rate of 50% or higher," according to one of the co-investigators, Christopher Twelves, MD, University of Leeds and Bradford, United Kingdom. In comparison, earlier studies by de Gramont and Goldberg combining 5-FU and oxaliplatin showed an overall response rate of 50% and 38%, respectively. In the XELOX study, the median progression- free survival was 7.7 months and the median overall survival was 19.5 months. The 1-year survival rate was 71%. Patient Profiles The study included 96 patients with metastatic colorectal cancer. Patients ranged in age from 34 years to 79 years, with a median age of 64 years. Eligible patients had measurable metastatic colorectal cancer, a Karnofsky performance status greater than 70, a life expectancy of at least 3 months, no prior therapy with oxaliplatin, capecitabine, or irinotecan(Drug information on irinotecan) (CPT-11, Camptosar), and no prior adjuvant therapy within 6 months of enrollment. Disease characteristics of the patients were typical of a first-line metastatic colorectal cancer trial: 64% colon tumors, 33% rectal tumors, and 3% rectosigmoid tumors. More than half of the patients (54%) had more than one metastatic site. Lung metastases were present in 32% of patients and liver metastases in 77%. Twenty-seven percent of patients had received prior adjuvant treatment. Capecitabine and oxaliplatin do not overlap in key toxicities. The safety data were consistent with prior studies with XELOX, and compare favorably with the safety profile of FOLFOX4 (fluorouracil, leucovorin, oxaliplatin). Overall, there was a low incidence of grade 3/4 treatment-related adverse events, and only three patients experienced grade 3 hand-foot syndrome. The most common grade 3/4 treatment-related adverse events were sensory neuropathy (17%), diarrhea (16%), and nausea/ vomiting (13%). Impressive Percentage Receive Full Dose Of particular importance was the fact that 50% of patients received full dose capecitabine/oxaliplatin throughout their treatment-an impressive percentage given the long duration of the treatment. "XELOX has comparable efficacy and safety to the FOLFOX regimens in firstline treatment of metastatic colorectal cancer, being highly active and safe, while requiring far less time of the patient." Dr. Van Cutsem concluded, Ongoing phase III trials are evaluating XELOX and comparing it to FOLFOX. The objective of these studies is to verify the ability of capecitabine to replace 5-FU/leucovorin as the backbone of advanced colorectal cancer therapy.