title: Factors predicting efficacy of oxaliplatin in combination with 5-fluorouracil (5-FU) +/- folinic acid in a compassionate-use cohort of 481 5-FU-resistant advanced colorectal cancer patients.
abstract: A statistical analysis was performed on the patient data collected from two compassionate-use programmes using oxaliplatin (Eloxatin(R)) + 5-fluorouracil (5-FU) +/- folinic acid (FA), to identify predictive factors for oxaliplatin-based salvage treatment in patients with 5-FU-resistant advanced colorectal cancer (ACRC). 481 5-FU-resistant ACRC patients, most with performance status < or = 2, > or = 3 involved sites, and > or = 2 prior lines of chemotherapy, received oxaliplatin + 5-FU +/- FA. Prognostic factors associated with overall response rate (ORR), time to progression (TTP) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. The ORR was 16% (95% CI: 13-20), the median TTP was 4.2 months (95% CI: 3.4-4.6), and the median OS was 9.6 months (95% CI: 8.6-10.6). The multivariate analysis indicated poor (> or = 2 WHO) performance status (PS), a large number of prior chemotherapy regimens (> or = 3), a low baseline haemoglobin level (< 10 g/dl), and a triweekly (vs biweekly) treatment administration schedule as significantly associated (P< 0.05) with a lower ORR. Sex (male), number of organs involved (> or =3) and alkaline phosphatase (AP) level (> or = 2 x the upper limit of normal) were associated (P< 0.05) with shorter TTP. Poor PS, a large number of organs involved, and elevated AP were independently and significantly correlated with shorter OS. Our analysis identified a relationship between efficacy results of oxaliplatin + 5-FU +/- FA treatment in 5-FU-resistant ACRC patients and baseline prognostic factors related to PS, extent of disease and number of prior regimens.
authors.affiliation: Cvitkovic et Associés Consultants, 18-20 rue Pasteur, 94278 Kremlin-Bicêtre, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Bensmaïne
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: A
authors.initials: A
authors.lastname: de Gramont
authors.forename: S
authors.initials: S
authors.lastname: Brienza
authors.forename: F
authors.initials: F
authors.lastname: Lévi
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: E
authors.initials: E
authors.lastname: François
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D011379:Prognosis; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil