ORLANDO-At a median follow- up of 51 months, data reported at ASCO from the X-ACT phase III trial of capecitabine(Drug information on capecitabine) (Xeloda) vs bolus fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin (LV) as adjuvant therapy for patients with Dukes' C colon cancer confirm that adjuvant capecitabine showed consistent benefits over bolus 5-FU/LV, with at least equivalent disease-free survival (DFS) and a better safety profile, Christopher Twelves, MD, said (abstract 3521). "The superior efficacy of capecitabine over 5-FU/LV in metastatic disease (response rate) has translated into superior efficacy in the adjuvant setting (relapse-free survival). These findings provide a very clear rationale for replacing 5-FU/LV with capecitabine in the adjuvant treatment of colon cancer," Dr. Twelves said. The X-ACT trial was undertaken to evaluate the efficacy of capecitabine vs 5-FU/LV after studies showed superior activity and improved safety for oral capecitabine compared with bolus 5-FU/LV in first-line metastatic colorectal cancer. The open-label, multinational, randomized, parallel-group study enrolled 1,987 patients with resected Dukes' C colon carcinoma. Patients were randomized to receive either oral capecitabine (1,250 mg/m2 twice daily on days 1-14, every 3 weeks) or IV 5-FU/LV (Mayo Clinic regimen: LV-20 mg/m2 + 5-FU-425 mg/m2 on days 1-5, every 4 weeks) for 24 weeks. Equivalent DFS, Better RFS The primary study endpoint was at least equivalence in DFS. Dr. Twelves said that the intent-to-treat analysis showed at least equivalence in terms of DFS between the treatment arms, with a strong trend toward superior DFS for capecitabine (hazard ratio [HR] = 0.87; 95% confidence interval [CI], 0.75-1.00; P =.0525). At a median follow- up of 53 months, reported following ASCO, 3-year DFS was 66% with capecitabine vs 62.9% with 5- FU/LV (hazard ratio 0.87; P = .055). Relapse-free survival was significantly better for capecitabine. The HR of 0.89 translates into a significant 14% reduction in risk of relapse with capecitabine. Capecitabine caused significantly (P < .001) less all-grade diarrhea, nausea/vomiting, stomatitis, alopecia, and neutropenia and less grade 3/4 neutropenia, stomatitis, and neutropenic fever/sepsis than 5-FU/LV. Capecitabine caused more nonlife-threatening hand-foot syndrome and hyperbilirubinemia than 5-FU/LV (P < .001). Dr. Twelves concluded, "Multivariate analysis showed that capecitabine treatment has a significant impact on DFS (P = .015). The improved safety profile of capecitabine in the adjuvant setting mirrors that observed in the metastatic setting. The high efficacy, improved safety, and convenience of capecitabine may increase the proportion of patients able and/or willing to benefit from adjuvant treatment." Adjuvant Xeloda Receives FDA Approval Since ASCO, the U.S. Food and Drug Administration (FDA) has approved Xeloda for use as single-agent adjuvant therapy following complete resection of the primary tumor for patients with Dukes' C colon cancer when treatment with fluoropyrimidine therapy alone is preferred. Approval was granted after review of data from the X-ACT trial (see page 6).