Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): Results from the European compassionate-use program

Purpose: To provide evidence for the therapeutic efficacy of oxaliplatin (E loxatin(R)) when given as a 2-6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU +/- FA) in patients with advanced c olorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm t he safety of the drug and its combination in an extended-access context. Patients and methods: Prescribing physicians were supplied oxaliplatin on a nominative compassionate-use basis, after obtaining informed consent. Euro pe-wide, 206 ACRC patients in 44 centers received 1168 cycles of chemothera py with oxaliplatin (80-100 mg/m(2) q 2 weeks or 100-135 mg/m(2) q 3 weeks) delivered as a short (2-6 hours) i.v. infusion, 177 of them (1026 cycles) receiving oxaliplatin + 5-FU +/- FA. Results: Oxaliplatin added to the 5-FU +/- FA regimens of 111 verified 5-FU -refractory patients (imaging and/or clinical proof of progression under pr ior 5-FU-based regimen), elicited objective responses in 25 of 98 evaluable patients, (ORR: 25.5%, 95% confidence interval (95% CI: 17-35). The median time to progression was 4.1 months (95% CI: 3.3-5.0) and the median overal l survival was 9.6 months (95% CI: 8.2-10.9). Differences in the toxicity p rofile of the oxaliplatin + 5-FU +/- FA combination appear related to admin istration modality, dose and schedule of the 5-FU-based regimen. Conclusions: The addition of oxaliplatin (2-6-hour i.v. infusion) to 5-FU /- FA regimens is active in ACRC patients with clinical resistance to fluor opyrimidines. The therapeutic index of oxaliplatin + 5-FU +/- FA combinatio ns administered as salvage therapy compares favorably with those reported i n recent phase II-III trials involving other new agents or combinations act ive in 5-FU-refractory ACRC patients.