title: A phase II study of capecitabine, irinotecan, and bevacizumab in patients with previously untreated metastatic colorectal cancer.
abstract: BACKGROUND
  Previous phase III studies raised concern about the safety of the combination of capecitabine and irinotecan in patients with metastatic colorectal cancer (mCRC). We conducted a single arm phase II study to evaluate the safety and efficacy of bevacizumab in combination with dose-reduced capecitabine and irinotecan in patients with previously untreated mCRC.
  
  
  METHODS
  Patients with previously untreated mCRC were eligible. Capecitabine was given at 1,000 mg/m2 orally twice daily for 14 days and dose was reduced to 750 mg/m2 for patients over 65. Irinotecan was given at 200 mg/m2 and bevacizumab was given at 7.5 mg/kg intravenously on day 1. The treatment cycle was repeated every 21 days. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival, response rate, and toxicity.
  
  
  RESULTS
  Fifty patients were enrolled, the median age was 58, and 54% were ECOG 0. The most common grade 3/4 adverse events included hand-foot syndrome (14%), neutropenia (12%), and diarrhea (10%). Response rate was 51% and disease control rate (response and stable disease) was 98%. Median PFS was 11.5 months (95% CI: 9.2-13.7), and 6 month PFS was 90% (95% CI: 77-98%).
  
  
  CONCLUSIONS
  With modest dose reductions, the combination of capecitabine, irinotecan, and bevacizumab was well tolerated and resulted in favorable outcomes for patients with previously untreated mCRC.
authors.affiliation: Department of Medical Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Renouf
authors.forename: Stephen
authors.initials: S
authors.lastname: Welch
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Moore
authors.forename: Monika K
authors.initials: MK
authors.lastname: Krzyzanowska
authors.forename: Jennifer
authors.initials: J
authors.lastname: Knox
authors.forename: Ronald
authors.initials: R
authors.lastname: Feld
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Liu
authors.forename: Helen
authors.initials: H
authors.lastname: MacKay
authors.forename: Jennifer
authors.initials: J
authors.lastname: Petronis
authors.forename: Lisa
authors.initials: L
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin