BRADFORD, United Kingdom- Oral capecitabine(Drug information on capecitabine) (Xeloda) has an improved safety profile as adjuvant therapy for Duke's C colon cancer compared with IV fluorouracil(Drug information on fluorouracil) (5-FU)/leucovorin, the Mayo Clinic regimen, according to a study reported by Chris Twelves, MD, University of Leeds and Bradford, United Kingdom (ASCO abstract 1182). This improved safety profile of capecitabine in the adjuvant setting mirrors that reported in the metastatic setting, he added. "These results are part of a planned safety analysis that was conducted 18 months after enrollment of the last patient on a phase III trial of capecitabine vs bolus 5-FU/leucovorin as adjuvant therapy for colon cancer (the X-ACT study)," Dr. Twelves said. "The results of the safety analysis demonstrated that oral capecitabine, as adjuvant treatment for Duke's C colon cancer, was associated with significantly less diarrhea, nausea and vomiting, stomatitis, alopecia, and grade 3/4 neutropenia," he added. Adjuvant IV 5-FU/leucovorin improves outcomes in colon cancer. Capecitabine does too, but it is a tumor-activated oral fluoropyrimidine. "Two large phase III studies demonstrated that capecitabine achieves superior activity and improved safety compared with IV 5-FU/ leucovorin as first-line therapy for metastatic colorectal cancer," Dr. Twelves reported. Oral Therapy Preferred The oral administration of capecitabine enables twice-daily dosing that mimics continuous infusion 5-FU. "Of particular importance is the fact that 9 out of 10 patients prefer oral chemotherapy to IV administration," Dr. Twelves noted. "Outpatient oral chemotherapy allows patients to live a more normal life while receiving adjuvant treatment. This activity and patient preference for oral chemotherapy justifies comparing capecitabine with 5-FU/leucovrin as adjuvant treatment of Dukes'C colon carcinoma." Phase III X-ACT Trial The X-ACT trial was an open-label, multinational, randomized, parallelgroup, phase III trial of adjuvant therapy for Duke's C colon cancer. Between November 1998 and November 2001, 1,987 patients were enrolled at 164 centers worldwide. The primary end point of the trial was noninferiority in disease-free survival, and secondary end points were 3-year survival, safety profile, and quality of life. To determine the safety profile, safety was continuously monitored during treatment plus 28 days afterwards in all patients who received at least one dose of study medication (n = 1,970). The baseline characteristics were well balanced in the two treatment arms. For example, the median age in the capecitabine group was 62, and in the 5-FU/leucovorin group, it was 63. Both groups experienced a similar low incidence of treatment-related withdrawals. Eighty-two percent of patients receiving capecitabine completed all eight cycles and 88% of patients on 5-FU/ leucovorin received all six cycles. In both groups, the median delivered dose per cycle was greater than 95% of the planned dose throughout the treatment. Fewer patients in the capecitabine arm required dose reductions due to adverse events (41% with capecitabine vs 44% with 5-FU/leucovorin). Fewer Dose Reductions Overall, fewer adverse events occurred in the capecitabine arm than in the 5-FU/ leucovorin arm (4,158 vs 4,665, respectively). There were fewer treatment-related grade 3/4 adverse events in the capecitabine arm than in the 5-FU/leucovorin arm (533 vs 560). There was significantly less stomatitis and neutropenia in the capecitabine arm, a low incidence of nausea and vomiting (3%) in both arms, and less neutropenia in the capecitabine arm. Dr. Twelves did note that "hand-foot syndrome was significantly more common with capecitabine, but it can be easily managed with dose interruption and when necessary, with dose modification." He said that hyperbilirubinemia was more common with capecitabine, but that this is a known side effect of fluoropyrimidines and is rarely associated with clinical or enzymatic abnormalities. Three treatment-related deaths occurred in the capecitabine arm vs four in the 5-FU/leucovorin. There was a low incidence of all-cause, 60-day mortality: five (0.5%) deaths in the capecitabine arm and four (0.4%) in the 5-FU/leucovorin arm. Dr. Twelves concluded a description of the safety analysis by stating, "There were fewer adverse events with capecitabine than with 5-FU/leucovorin, and capecitabine was associated with fewer life-threatening adverse events. The improved safety profile of capecitabine in the adjuvant setting mirrors that in the metastatic setting. A notable difference in the capecitabine safety profile in the adjuvant and metastatic settings is less nausea/ vomiting in the adjuvant setting, suggesting that increased nausea/vomiting in the metastatic setting is disease-related."