title: Capecitabine plus oxaliplatin and irinotecan regimen every other week: a phase I/II study in first-line treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  A phase I/II study was performed to determine the safety and activity of a capecitabine plus oxaliplatin and irinotecan (COI) regimen using capecitabine concurrently with oxaliplatin and irinotecan in previously untreated patients with metastatic colorectal cancer.
  
  
  METHODS
  Patients received irinotecan on day 1, oxaliplatin (85 mg/m(2)) on day 2 and capecitabine (1000 mg/m(2) orally twice daily) on days 2-6 of a biweekly schedule. Three dose levels ranging from 150 to 180 mg/m(2) were explored for irinotecan in sequential cohorts of three to six patients. Once the recommended dose was determined, a total of 28 eligible patients were planned at this dose level.
  
  
  RESULTS
  Thirty-eight patients received a median of six cycles. The recommended phase II dose of irinotecan was 180 mg/m(2). Toxicity was manageable: the most common severe toxicities were diarrhoea (24%) and nausea (16%). Of 27 assessable patients treated at the recommended dose, 17 achieved a partial response (overall response rate (ORR) 63%; 95% confidece interval (CI), 44 to 78%), with eight patients undergoing liver metastasectomy. Estimated progression-free survival and overall median survival were 8.5 and 23.5 months, respectively.
  
  
  CONCLUSIONS
  Biweekly COI is feasible and active. Tolerability and ease of administration make the regimen well suited for downsizing hepatic colorectal metastases before curative surgery.
authors.affiliation: Medical Oncology Unit 2, Fondazione IRCCS 'Istituto Nazionale Tumori', Milan, Italy. emilio.bajetta@istitutotumori.mi.it
authors.forename: E
authors.initials: E
authors.lastname: Bajetta
authors.forename: L
authors.initials: L
authors.lastname: Celio
authors.forename: E
authors.initials: E
authors.lastname: Ferrario
authors.forename: M
authors.initials: M
authors.lastname: Di Bartolomeo
authors.forename: A
authors.initials: A
authors.lastname: Denaro
authors.forename: K
authors.initials: K
authors.lastname: Dotti
authors.forename: M
authors.initials: M
authors.lastname: Mancin
authors.forename: R
authors.initials: R
authors.lastname: Bajetta
authors.forename: A
authors.initials: A
authors.lastname: Colombo
authors.forename: S
authors.initials: S
authors.lastname: Pusceddu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001707:Biopsy, Needle; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D016001:Confidence Intervals; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008297:Male; D020714:Maximum Tolerated Dose; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome