A randomized phase III trial comparing mitomycin-C plus short-term doxifluridine (Mf) versus mitomycin-C plus long-term doxifluridine plus cisplatin (MFP) after curative resection of advanced gastric cancer (AMC 0201) (NCT00296335)

Abstract

4531 Background: Despite a continuing debate on the role of adjuvant chemotherapy, several studies have suggested that mitomycin-C (M) plus fluoropyrimidine (f) could improve the outcome of curatively resected advanced gastric cancer (AGC) patients (pts). To improve further the adjuvant Mf chemotherapy, we have prolonged the administration of oral fluoropyrimidine (F) and added cisplatin (P) to Mf (MFP) and performed a phase III randomized trial to determine whether this strategy could improve the 3 year relapse free survival rate (3yRFSR) in curatively resected AGC pts (HR=0.63, α=0.05, β=0.1). Methods: Three to 6 wks after R0 resection, the pts who had postoperative stage II-IV were randomized to receive either Mf or MFP adjuvant chemotherapy. For Mf group, 20 mg/m2 of M was iv injected and 4 wks later, 460–600 mg/m2/day of doxifluridine was administered orally for 3 months. For MFP group, the administration of doxifluridine was extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of cisplatin were added to Mf. Results: Between Feb 2002 and Aug 2006, a total of 871 pts were randomized (435 in Mf, 436 in MFP). Sixteen pts were excluded because of ineligibility (11 in Mf, 5 in MFP). Postoperative stages were II in 51.0%, IIIA in 31.1%, IIIB in 9.4%, and IV in 8.5% of pts. In Nov. 2007 after a median follow up of 3.2 yrs, there was no difference in 3yRFSR between the two groups (67.0% in Mf and 64.9% in MFP). Difference in overall survival (OS) was also insignificant; 3yOSR was 75.8% in Mf and 72.5% in MFP. The treatments were well tolerated in both groups. And, 92.9% of Mf and 71.6% in MFP could complete the planned schedule of treatment. Grade 3/4 neutropenia was more common in MFP (34%) than in Mf (9%). Grade 3/4 thrombocytopenia was rare and similar in both arms (3.6% in both groups). Vomiting of grade ≥2 was more common in MFP (23.2%) than in Mf (12.2%). There was no treatment-related death. Conclusions: Prolongation of doxifluridine administration and addition of cisplatin to adjuvant chemotherapy with mitomycin-C plus 3 months of doxifluridine could be safely performed but did not improve the treatment outcome in curatively resected AGC pts. No significant financial relationships to disclose.