Kang, Yoon-Koo; Yook, Jeong Hwan; Chang, Heung-Moon; Ryu, Min-Hee; Yoo, Changhoon; Zang, Dae Young; Lee, Jae-Lyun; Kim, Tae Won; Yang, Dae Hyun; Jang, Se Jin; Park, Young Soo; Lee, Young Jack; Jung, Hwoon-Yong; Kim, Jin-Ho; Kim, Byung Sik
Cancer chemotherapy and pharmacology
2014Jan ; 73 ( 1 ) :139-49.
PMID : 24162381
ÀúÀÚ »ó¼¼Á¤º¸
Kang, Yoon-Koo -
Yook, Jeong Hwan -
Chang, Heung-Moon -
Ryu, Min-Hee -
Yoo, Changhoon -
Zang, Dae Young -
Lee, Jae-Lyun -
Kim, Tae Won -
Yang, Dae Hyun -
Jang, Se Jin -
Park, Young Soo -
Lee, Young Jack -
Jung, Hwoon-Yong -
Kim, Jin-Ho -
Kim, Byung Sik -
ABSTRACT
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.
Mitomycin-C, Doxifluridine, Cisplatin, Intraperitoneal chemotherapy, Adjuvant chemotherapy, Advanced gastric cancer
MESH
Adult, Aged, Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use, Chemotherapy, Adjuvant, Cisplatin/administration & dosage, Female, Floxuridine/administration & dosage, Humans, Male, Middle Aged, Mitomycin/administration & dosage, Neoplasm Recurrence, Local, Stomach Neoplasms/*drug therapy/mortality/surgery
¸µÅ©