Six months versus twelve months of capecitabine as adjuvant chemotherapy for stage III (Dukes' C) colon cancer: Initial safety report for the open-label randomized phase III study (JFMC37-0801).

Abstract

3607 Background: The standard treatment duration of adjuvant chemotherapy (CT) in patients (pts) with stage III colon cancer is 6 months. On the other hand, no clinical trial showed the optimal treatment duration of oral chemotherapeutic agents in adjuvant setting for colon cancer. Sargent et al have reported that 83% of recurrences in stage II and III pts have occurred within the first 3 years after surgery and peak was observed around one year after surgery. Therefore, to clarify the benefit of 12 months administration of Capecitabine, we designed randomized phase III trial for a comparison of 6 months treatment and 12 months treatment of capecitabine as adjuvant CT for stage III colon cancer. Methods: JFMC37 is a multicenter, randomized Phase III trial. Patients with fully resected Stage III colon or recto sigmoid cancer were eligible. Capecitabine was administered orally as tablets, 2,500 mg/m²/day for 14 days followed by a 7-days rest. Treatment is continued to 8 cycles (6 months) in arm A (A) or 16 cycles (12 months) in arm B (B). Patients were randomized 1:1 to A or B. Data size was estimated by disease free survival as primary endpoint. The statistical design is based on superiority hypothesis; 5-yrs DFS is 60% in arm A, 67% in arm B ;unilateral α=0.05, 1-β=0.8;and planed accrual is 1200 pts. Results: Between September 2008 to December 2009, 1304 patients were enrolled and then randomized. Both arms were well balanced for mean age: (A) 64.1, (B) 63.8; ECOG PS (%0/1): (A) 95.0/5.0, (B) 97.1/2.9; involvement of lymph nodes (%N0/N1/N2): (A) 77.1/19.9/3.1, (B) 76.6/19.7/3.7. Treatment completion rate for A and B were 68.2% and 43.4%. Incidences of serious adverse events (SAEs) over 1% were neutropenia: (A) 2.6%, (B) 3.8%, diarrhea: (A) 2.9%, (B) 2.1%, loss of appetite: (A) 1.3%, (B) 1.0%, fatigue: (A) 1.8%, (B) 1.2%, hand-hoot syndrome: (A) 16.4%, (B) 22.1%. Conclusions: There were no obvious differences in SAEs between arm A and arm B. Although twelve months of capecitabine showed a tendency to increase G3/4 hand-foot syndrome, we concluded that incidence of SAEs were acceptable and comparable to previously report.