title: A Phase II Trial of Combined Chemotherapy with Oral S-1 and 24-Hour Infusions of Irinotecan plus Bevacizumab in Patients with Metastatic Colorectal Cancer.
abstract: OBJECTIVE
  Protracted low-dose infusion of irinotecan has been suggested to enhance antitumor activity. A phase II study was conducted to evaluate the safety and efficacy of oral S-1 combined with 24-hour infusion of irinotecan and intravenous bevacizumab for metastatic colorectal cancer (MCRC).
  
  
  METHODS
  The subjects were 79 patients with MCRC; 57 were chemotherapy naïve. Irinotecan (125 mg/m(2)) was administered as a 24-hour infusion on days 1 and 15, S-1 (80 mg/m(2)) was administered orally on days 1-14, and bevacizumab (5.0 mg/kg) was given on days 1 and 15. The treatment was repeated every 4 weeks.
  
  
  RESULTS
  Median follow-up was 20.0 months, and the mean number of cycles was 7. The overall response rate was 79.7% (95% CI, 69.2-88.0), 86.0% (95% CI, 74.2-93.7) for first-line and 63.6% (95% CI, 40.7-82.8) for second-line treatment. The median progression-free survival was 16.4 months (95% CI, 13.9-21.0) for first-line and 9.4 months (95% CI, 4.9-16.5) for second-line treatment. The median overall survival was not reached. Grade 3-4 toxicities were neutropenia (43%), leukopenia (20.3%), anorexia (19.0%), and diarrhea (10.1%). Toxicity was tolerable.
  
  
  CONCLUSIONS
  Combination chemotherapy with oral S-1 and biweekly 24-hour infusions of irinotecan plus bevacizumab appears to be highly active and well tolerated both as first-line and second-line chemotherapy for MCRC.
authors.affiliation: Department of Surgery, Tokai University, Isehara, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Sadahiro
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kazutake
authors.initials: K
authors.lastname: Okada
authors.forename: Gota
authors.initials: G
authors.lastname: Saito
authors.forename: Akemi
authors.initials: A
authors.lastname: Kamijo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D000068258:Bevacizumab; D010094:Oxonic Acid; D000077146:Irinotecan; D002166:Camptothecin