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

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 less than or equal to 2, greater than or equal to 3 involved sites, and greater than or equal to 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% Cl: 13-20), the median TTP was 4.2 months (95% Cl: 3.4-4.6), and the median OS was 9.6 months (95% Cl: 8.6-10.6). The multivariate analysis indicated poor (greater than or equal to 2 WHO) performance status (PS), a large number of prior chemotherapy regimens (greater than or equal to 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 (greater than or equal to3) and alkaline phosphatase (AP) level (greater than or equal to 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. (C) 2001 Cancer Research Campaign.