title: Oxaliplatin with high-dose leucovorin and infusional 5-fluorouracil in irinotecan-pretreated patients with advanced colorectal cancer (ACC).
abstract: The purpose of this study was to evaluate the efficacy and tolerance of the bimonthly administration of oxaliplatin in combination with high-dose leucovorin and infusional 5-fluorouracil (5-FU) (FOLFOX2 regimen) in patients with advanced colorectal cancer (ACC) who did not respond or whose disease progressed within 3 months after front-line treatment with CPT-11-containing regimens. Forty-one patients with ACC who did not respond or whose disease progressed after front-line treatment with CPT-11 + 5-FU/leucovorin were enrolled. Oxaliplatin was administered at the dose of 100 mg/m2 on day 1 as a 2-hour infusion simultaneously but through different lines with leucovorin (500 mg/m2 on days 1 and 2); 5-FU was given at the dose of 1,750 mg/m2/d as a 22-hour continuous intravenous infusion on days 1 and 2. The regimen was repeated every 2 weeks. In an intention-to-treat analysis, complete response was achieved in one (2.4%) and partial response in six (14.6%) patients (overall response rate: 17%; 95% CI: 5.56-28.59%); stable disease and progressive disease were observed in 15 (36.6%) and in 19 (46.31%) patients, respectively. The median duration of response and the median time to tumor progression were 6 and 8.5 months, respectively. The median overall survival was 12 months and the probability for 1-year survival was 42.9%. Grade III/IV neutropenia occurred in 17 (41%) patients and febrile neutropenia developed in one of them (2%). There was no treatment-related death. Peripheral neuropathy greater than or equal to grade II occurred in 24 (58%) patients. Other toxicities were relatively mild. The bimonthly administration of oxaliplatin in combination with high-dose leucovorin and 48-hour continuous infusion of 5-FU is a relatively active and well-tolerated regimen for patients with ACC resistant or refractory to CPT-11 + 5-FU (continuous infusion)/leucovorin.
authors.affiliation: Department of Medical Oncology, University General Hospital of Heraklion, Crete, Greece.
authors.forename: Charalambos
authors.initials: C
authors.lastname: Kouroussis
authors.forename: John
authors.initials: J
authors.lastname: Souglakos
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavroudis
authors.forename: Savvakis
authors.initials: S
authors.lastname: Papadouris
authors.forename: Stylianos
authors.initials: S
authors.lastname: Kakolyris
authors.forename: Sophia
authors.initials: S
authors.lastname: Agelaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Kalbakis
authors.forename: Christos
authors.initials: C
authors.lastname: Panopoulos
authors.forename: Nikos
authors.initials: N
authors.lastname: Vardakis
authors.forename: Evanthia
authors.initials: E
authors.lastname: Sarra
authors.forename: Vassilis
authors.initials: V
authors.lastname: Georgoulias
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016879:Salvage Therapy; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D009944:Organoplatinum Compounds; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin