title: Capecitabine, oxaliplatin and irinotecan in combination, with bevacizumab (COI-B regimen) as first-line treatment of patients with advanced colorectal cancer. An Italian Trials of Medical Oncology phase II study.
abstract: BACKGROUND
  A dose-finding phase I/II trial that evaluated the maximum tolerated doses of a combination of three drugs with irinotecan, oxaliplatin and capecitabine (COI regimen) has been conducted in patients with metastatic colorectal cancer (mCRC). In this study the safety and activity of the combination of COI regimen plus bevacizumab (COI-B) were assessed.
  
  
  METHODS
  Patients judged to be unresectable for metastatic disease, were enrolled in a phase II, open-label study and treated with the combination of bevacizumab (5mg/kg on day 1) and COI regimen (irinotecan 180mg/mq on day 1, oxaliplatin 85mg/mq on day 2, capecitabine 2000mg d2-6; q14) as first-line treatment. Induction treatment was administered for a maximum of 8 cycles, followed by maintenance treatment with bevacizumab (7.5mg/kg on d1, q21) until progression.
  
  
  RESULTS
  Fifty-one patients were enrolled in six Italian centres. The primary end-point of overall response rate was met, reaching the value of 62% in the per-protocol population and 57% in the intent-to-treat population, patients with stable disease were also taken into account, the clinical benefit rate was 94%. In the intention-to-treat population, median progression-free and overall survivals were 10.3 and 22 months, respectively. Toxicity was different from 5-fluorouracil-based triplet regimens, with 31% of severe diarrhoea, but a low incidence of grade 3/4 neutropenia (6%) and mucositis (4%).
  
  
  CONCLUSIONS
  Our results show the feasibility and promising activity of the combination of capecitabine, oxaliplatin, irinotecan and bevacizumab.
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy. Electronic address: maria.dibartolomeo@istitutotumori.mi.it.
authors: Maria
authors: M
authors: Di Bartolomeo
authors: Ospedale Misericordia e Dolce, Prato, Italy.
authors: Andrea
authors: A
authors: Ciarlo
authors: A.O. Valtellina e Valchiavenna, Sondrio, Italy.
authors: Alessandro
authors: A
authors: Bertolini
authors: A.O. Treviglio, BG, Italy.
authors: Sandro
authors: S
authors: Barni
authors: A.O. Saronno, Italy.
authors: Claudio
authors: C
authors: Verusio
authors: Medical Oncology Department, Mantova, Italy.
authors: Enrico
authors: E
authors: Aitini
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Filippo
authors: F
authors: Pietrantonio
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Roberto
authors: R
authors: Iacovelli
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Katia Fiorella
authors: KF
authors: Dotti
authors: Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Claudia
authors: C
authors: Maggi
authors: Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
authors: Federica
authors: F
authors: Perrone
authors: Policlinico Monza, Italy.
authors: Emilio
authors: E
authors: Bajetta
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin
keywords: Bevacizumab; Capecitabine; Colorectal cancer; Triplet chemotherapy