Postoperative adjuvant chemotherapy for grossly serosa-positive advanced gastric cancer: A randomized phase III trial of intraperitoneal cisplatin and early mitomycin-C plus long-term doxifluridine plus cisplatin (iceMFP) versus mitomycin-C plus short- term doxifluridine (Mf) (AMC 0101) (NCT00296322)
Authors: Y. Kang, H. Chang, D. Zang, J. Lee, T. Kim, D. Yang, S. Jang, J. Yook, S. Oh, B. Kim
Journal: Journal of Clinical Oncology (2008)

LBA4511 Background: To improve the postoperative adjuvant chemotherapy in serosa-involving AGC, we have adopted the strategies of intraperitoneal and early start of chemotherapy, as well as prolongation of oral fluoropyrimidine and addition of cisplatin (P) to Mf regimen. This phase III trial was designed to determine whether experimental iceMFP could improve 3 year relapse free survival rate (3yRFSR) compared to control Mf. (For HR 0.66, α=0.05, β=0.2, N=527 with 192 events) Methods: Pts whose tumor were grossly seroa-positive and able to be resected curatively were randomized during operation to receive either Mf or iceMFP. Pts with postoperative pathologic stage I or IV (M1) were excluded after surgery. For Mf, 20 mg/m2 of mitomycin-C (M) was injected 3–6 wks after surgery and 4 wks later, 460–600 mg/m2/day of doxifluridine was administered orally for 3 months. For iceMFP, 100 mg of P in 1 L of saline was administered intraperitoneally for 2 h during surgery and 15 mg/m2 of M was injected 1 day after surgery. Doxifluridine was started 4 wks after surgery and extended for a total of 12 months and 6 shots of monthly 60 mg/m2 of P were added. Results: Between Oct 2001 and Apr 2007, a total of 640 pts were randomized (318 in Mf, 322 in iceMFP). One hundred and nineteen pts (60 in Mf, 59 in iceMFP) were excluded because of postoperative stage I in 90, IV (M1) in 13, positive resection margin in 10, and others in 6. Therefore, a total of 521 pts (258 in Mf, 263 in iceMFP) were eligible for intent-to- treat analysis. Postoperative stages were II in 33.4%, IIIA in 31.9%, IIIB in 17.5%, and IV in 17.3% of pts. Rates of postoperative complications were similar in 2 groups (14% in Mf, 10% in iceMFP). The treatments were well tolerated in both groups with more grade 3- 4 neutropenia (41% vs 19%) and grade 3 vomiting (16% vs 5%) in iceMFP group. There was no treatment-related death. With a median follow-up of 3.5 years, a total of 229 events (relapse or death) have been observed. As compared with Mf group, iceMFP group had a higher likelihood of relapse free survival (RFS) (HR, 0.70; 95% C.I. 0.54 - 0.90; p=0.0063; 3yRFSR 60.2% vs 50.0%) and of overall survival (OS) (HR, 0.71; 95% C.I. 0.53 - 0.95; p=0.0209; 3yOSR 71.2% vs 59.6%). Conclusions: Postoperative iceMFP chemotherapy could significantly improve the RFS and OS in pts with grossly serosa-positive AGC, compared with Mf chemotherapy. Considering no benefit of adding cisplatin and prolongation of oral doxifluridine to Mf chemotherapy in curatively resected AGC pts (AMC0201, abstr No.6, ASCO-GI 2008), intraperitoneal cisplatin and/or early start of chemotherapy seemed to be responsible for the improved efficacy of iceMFP chemotherapy in this study. No significant financial relationships to disclose.