title: Phase II study of biweekly irinotecan and mitomycin C combination therapy in patients with fluoropyrimidine-resistant advanced colorectal cancer.
abstract: OBJECTIVE
  Experimental studies have shown that mitomycin C (MMC) acts synergistically with irinotecan. We evaluated the antitumor activity and toxicity of a combination of irinotecan and MMC in patients with metastatic colorectal cancer resistant to fluoropyrimidines.
  
  
  METHODS
  Eligible patients had evidence of tumor progression while receiving fluoropyrimidine-based regimens or had disease recurrence within 6 months after the completion of adjuvant treatment with fluoropyrimidines. Irinotecan (150 mg/m(2)) and MMC (5 mg/m(2)) were administered on days 1 and 15 of a 28-day cycle. Treatment was repeated every 4 weeks.
  
  
  RESULTS
  Among the 41 patients enrolled, 37 (90%) had received previous chemotherapy for metastatic disease, and 4 had received adjuvant chemotherapy alone. Objective responses were observed in 14 patients (34%, 95% confidence interval 20-49%). The median time to progression was 4.2 months, and the median survival time was 11.9 months. The study treatment was well tolerated; the median number of cycles received was four. Grade 3 or 4 neutropenia, the most common toxic effect, occurred in 20 patients (49%). Grade 3 or 4 thrombocytopenia occurred in four patients (10%) and grade 3 diarrhea in one patient.
  
  
  CONCLUSIONS
  Our results suggest that irinotecan and MMC combination therapy is effective and well tolerated in patients with fluoropyrimidine-resistant metastatic colorectal cancer. Further clinical investigation of this regimen is warranted.
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. yayamada@ncc.go.jp
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Ichinosuke
authors.initials: I
authors.lastname: Hyodo
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Arai
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Denda
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ambo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage
chemical_list: D016685:Mitomycin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin