Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric
cancer: results from a phase 3 randomized trial (AMC0101).
Author(s): Kang YK(1), Yook JH, Chang HM, Ryu MH, Yoo C, Zang DY, Lee JL, Kim TW, Yang DH,
Jang SJ, Park YS, Lee YJ, Jung HY, Kim JH, Kim BS.
Affiliation(s): Author information:
(1)Department of Oncology, Asan Medical Center, University of Ulsan College of
Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea,
ykkang@amc.seoul.kr.
Publication date & source: 2014, Cancer Chemother Pharmacol. , 73(1):139-49
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.
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