Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6)

For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the ad dition of oxaliplatin (85 or 100 mg/m(2)) to bimonthly LV-5-FU has given a response rate of 20-46%. The highest response rate has been observed with o xaliplatin 100 mg/m(2) (FOLFOX2). The present phase II study (FOLFOX6) infu sed oxaliplatin (100 mg/m(2)) with LV (400 mg/m(2)) as a 2-h infusion on da y 1, followed by bolus 400 mg/m(2) and a 46-h infusion (2.4-3 g/m(2)) of 5- FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial resp onses (95% confidence interval: 15-58),27 (45%) had stable disease, 15 (25% ) experienced disease progression and 2 (3%) had non-measurable disease. Fr om the start of FOLFOX6, median progression-free survival was 5.3 months an d median survival 10.8 months. Front the 448 cycles analysed, NCI-CTC grade 3-4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, dia rrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 ( 46%) patients experienced grade 3-4 toxicities. Because of toxicity, only 3 6% of the patients received greater than or equal to 90% of the scheduled o xaliplatin dose intensity. FOLFOX6 was active in pretreated patients resist ant to LV-5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity a nd a lower 5-FU dose. (C) 1999 Elsevier Science Led. All rights reserved.