Six months compared with 12 months of capecitabine as adjuvant chemotherapy for stage III (Dukes' C) colon cancer: Rationale for the open-label randomized phase III study, JFMC37-0801.
517 Background: The standard duration of adjuvant chemotherapy (CT) in patient with stage III colorectal cancer is 6 months. On the other hand, no clinical trial which investigate an optimal duration of oral chemotherapeutic agents has yet been implemented for adjuvant treatments. According to the ACCENT database (Sargent, et al. J Clin Oncol 27: 872- 877, 2009), 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. Also, single-agent FU-based adjuvant CT reduced the hazard rate of OS, DFS, and TTR, although the peak of events around one year was still remained especially for stage III pts. We analyzed the data of recurrent risk of curatively resected colon cancer pts provided by JFMC7-1-7-2-15, X-ACT. Surgery alone group and 6 months CT (5FU/LV or capecitabine [Cape]) showed highest peak between 12 months to 18 months after surgery, but 12 months oral 5-FUs group did not show recurrence peak between 12 months to 18 months after surgery. Therefore, to clarify the benefit of 12 month administration of Cape, we planned a phase III randomized trial for a comparison of 6 months treatment and 12 months treatment. Methods: JFMC37 is a multicenter, randomized phase III trial. Patients with fully resected stage III colon or recto sigmoid cancer were eligible. Patients were randomized 1:1 to receive Cape of 6 months (arm A) or Cape of 12 months (arm B). Primary endpoint is disease-free survival. 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, 1,304 pts were randomized. Patients characteristics are (armA/armB); number 653/651, gender M352-F301/M343-F308, median age 65 years/65 years, ECOG PS=0-1 620-33/632-19, involvement of lymph nodes=N0-N1-N2 503-130-20/499-128-24. There were no differences in baseline characteristics between arm A and arm B. Conclusions: This trial is expected to show if 1 year adjutant chemotherapy with capecitabine can reduce the peak of recurrence in 1 year and provide long-term OS benefit. [Table: see text]