Capecitabine Equal to Bolus 5-FU/LV in Adjuvant Therapy for Colon Cancer

NEW ORLEANS-As adjuvant therapy for colon cancer, oral treatment with capecitabine(Drug information on capecitabine) (Xeloda) is at least equivalent to an intravenously administered bolus of 5-fluorouracil plus leucovorin (5-FU/LV), the longterm standard of care. This is the principal conclusion drawn from the phase III X-ACT Trial (Xeloda in Adjuvant Colon Cancer Therapy). Jim Cassidy, MD, of the University of Glasgow, Scotland, presented the results at the 40th Annual Meeting of the American Society for Clinical Oncology (abstract 3509). "In my opinion," Dr. Cassidy said, "capecitabine should replace bolus 5-FU/LV in the adjuvant treatment of Dukes' C colon cancer." The multicenter trial, involving investigators in 164 centers, enrolled 1,987 patients with resected Dukes' C colon cancer. Within 8 weeks of tumor resection, patients were randomized to oral capecitabine (1,250 mg/ m² twice daily for 14 days, every 3 weeks) or to the Mayo Clinic regimen of intravenous 5-FU/LV (5-FU 425 mg/m²/LV 20 mg/m² days 1 to 5, every 4 weeks); treatment continued for 24 weeks, for a total of eight cycles of capecitabine and six cycles of 5-FU/ LV. Patients were followed for a median of 3.8 years. In both groups, the great majority completed the full course of treatment (84% in the capecitabine arm vs 88% in the 5-FU/ LV arm), although dose management was required, with 57% of capecitabine patients and 52% of 5-FU/LV patients requiring dose reduction, delay, or interruption at some point during the trial. Dr. Cassidy pointed out that the oral formulation of capecitabine was particularly advantageous in facilitating this dosage management, permitting patient involvement in maintenance of the protocol. The principal endpoint was disease- free survival (relapse-free survival plus all deaths from other causes), with the aim being to demonstrate that oral capecitabine was at least equivalent in efficacy to 5-FU/LV; in addition, secondary efficacy measures included overall survival and relapsefree survival (relapses or new colon cancer plus all deaths due to colon cancer or treatment). In the intent-to-treat analysis, disease- free survival with capecitabine was not only equivalent to 5-FU/LV, but at 3 years showed a definite trend toward superiority-64.2% vs 60.6%, hazard ratio (HR) 0.87-almost reaching statistical significance (P = .0528). This was confirmed in the per-protocol population, in which the hazard ratio for disease-free survival for patients on capecitabine was 0.89. Superior Relapse-Free Survival Similar treatment-related differences, in favor of capecitabine, were also observed in the intent-to-treat analysis for 3-year relapse-free survival (65.5% vs 61.9%, HR = 0.86), which was significant at P = .0407, and overall survival (81.3% vs 77.6%, HR = 0.84, P = .0706). Subgroup analysis also confirmed the superiority of capecitabine, irrespective of gender, age group, nodal status, and level of carcinoembryonic antigen (CEA). Oral capecitabine also showed an improved safety profile, compared with the traditional 5-FU/LV regimen, with significantly fewer adverse events in nearly all categories, including diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia (P < .001 in all cases). This improved safety profile was also maintained in patients over 70 years, a group whose greater sensitivity often precludes receiving full treatment regimens. The sole exception in the adverse event profile was the greater frequency in the capecitabine group of handfoot syndrome, which was readily managed with dose reduction, Dr. Cassidy said. The X-ACT trial has demonstrated that treatment with oral capecitabine leads to superior relapse-free survival, shows clear trends toward improved disease-free and overall survival, and has a superior safety profile, when compared to the traditional standard of intravenous 5-FU/LV, Dr. Cassidy concluded. Moreover, he said, these advantages are also accompanied by the convenience of oral dosing.