title: Combined irinotecan, oxaliplatin and 5-fluorouracil in patients with advanced colorectal cancer. a feasibility pilot study.
abstract: OBJECTIVE
  To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC).
  
  
  METHODS
  A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1-4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group.
  
  
  RESULTS
  Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3-4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% CI: 1.07-76.20) and 0.23-fold lower in the IV-FUFOL/IRI250 group (95% CI: 0.05-0.97).
  
  
  CONCLUSIONS
  This combination seems to have substantial activity in ACC. Overall toxicity was unacceptable in the IA-FU and IRI300 groups, with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m2 day 1), IV CPT-11 (250 mg/m2 day 1) and IV 5-FU 2.6 g/m2 with IV leucovorin (500 mg/m2 days 1 and 15) was favorable and deserves further investigation.
authors.affiliation: Department of Oncology, Division of Medical Oncology, Clínica Universitaria de Navarra, University of Navarra, Navarra, Spain. calvo@hsanjaime.com
authors.forename: Emiliano
authors.initials: E
authors.lastname: Calvo
authors.forename: Javier
authors.initials: J
authors.lastname: Cortés
authors.forename: María
authors.initials: M
authors.lastname: González-Cao
authors.forename: Javier
authors.initials: J
authors.lastname: Rodríguez
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Aramendía
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández-Hidalgo
authors.forename: Salvador
authors.initials: S
authors.lastname: Martín-Algarra
authors.forename: José Esteban
authors.initials: JE
authors.lastname: Salgado
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.forename: Jokin
authors.initials: J
authors.lastname: de Irala
authors.forename: Antonio
authors.initials: A
authors.lastname: Brugarolas
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; 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* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010865:Pilot Projects; D015996:Survival Rate; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin