PURPOSE: To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study. METHODS: We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m(2)) at 3-6 weeks after surgery and oral doxifluridine (460-600 mg/m(2)/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m(2)) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m(2)). The primary endpoint was 3-year recurrence-free survival (RFS). RESULTS: A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio [HR] 0.70; 95 % confidence interval [CI] 0.54-0.90; p = 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53-0.95; p = 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications. CONCLUSION: The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy.
RCT Entities:
PURPOSE: To improve the efficacy of adjuvant chemotherapy with mitomycin-C and fluoropyrimidine (Mf) in gastric cancer, we designed a new regimen (iceMFP) and investigated in a phase III study. METHODS: We randomly assigned 640 patients with resectable and macroscopically recognizable serosa-invading gastric cancer to Mf or iceMFP group during operation. The Mf consisted of intravenous mitomycin-C (20 mg/m(2)) at 3-6 weeks after surgery and oral doxifluridine (460-600 mg/m(2)/day) starting 4 weeks after the administration of mitomycin-C and continuing for 3 months. The iceMFP consisted of intraoperative intraperitoneal cisplatin (100 mg), intravenous mitomycin-C (15 mg/m(2)) on postoperative day 1, followed by oral doxifluridine for 12 months, and six monthly intravenous cisplatin (60 mg/m(2)). The primary endpoint was 3-year recurrence-free survival (RFS). RESULTS: A total of 521 patients (258 in Mf, 263 in iceMFP) were eligible for analysis after excluding patients with stage I disease, distant metastasis, or R1 resection. With a median follow-up of 3.5 years, the iceMFP group had a higher RFS (hazard ratio [HR] 0.70; 95 % confidence interval [CI] 0.54-0.90; p = 0.006; 3-year RFS 60 % vs. 50 %) and overall survival (HR 0.71; 95 % CI 0.53-0.95; p = 0.02; 3-year overall survival, 71 vs. 60 %) compared with the Mf group. This was confirmed at extension analysis after a median 6.6 years of follow-up. Both regimens were well tolerated with no differences in surgical complications. CONCLUSION: The efficacy of adjuvant Mf was significantly improved by the additional therapeutic strategies of iceMFP. Considering negative results of AMC0201, these suggest that early initiation of chemotherapy and/or intraperitoneal cisplatin played a distinct role in the improved efficacy.
Authors: Ivy N Haskins; Matthew D Kroh; Richard L Amdur; Jeffrey L Ponksy; John H Rodriguez; Khashayar Vaziri Journal: J Gastrointest Surg Date: 2017-07-25 Impact factor: 3.452
Authors: Astrid E Slagter; Edwin P M Jansen; Hanneke W M van Laarhoven; Johanna W van Sandick; Nicole C T van Grieken; Karolina Sikorska; Annemieke Cats; Pietje Muller-Timmermans; Maarten C C M Hulshof; Henk Boot; Maartje Los; Laurens V Beerepoot; Frank P J Peters; Geke A P Hospers; Boudewijn van Etten; Henk H Hartgrink; Mark I van Berge Henegouwen; Grard A P Nieuwenhuijzen; Richard van Hillegersberg; Donald L van der Peet; Heike I Grabsch; Marcel Verheij Journal: BMC Cancer Date: 2018-09-10 Impact factor: 4.430