title: A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial).
abstract: BACKGROUND
  Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer.
  
  
  METHODS
  Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6 months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5 mg/m(2)) and CPT-11 (150 mg/m(2)) administered i.v. every 2 weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR.
  
  
  RESULTS
  Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16-42%). The median time to progression was 4.1 months, and the median survival time was 10 months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively.
  
  
  CONCLUSIONS
  Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. thamaguc@ncc.go.jp
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takiuchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Iwase
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002945:Cisplatin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D007564:Japan; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D016879:Salvage Therapy; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D016685:Mitomycin; D000077146:Irinotecan; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin; D008727:Methotrexate