A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with 5-fluorouracil and folinic acid (Mayo Clinic regimen) in previouslyuntreated metastatic colorectal cancer patients

The aim of this study was to examine the efficacy and safety of both oxalip latin as a single agent and oxaliplatin in combination with daily x 5 bolus 5-fluorouracil and folinic acid (5-FU/FA, Mayo clinic regimen) in the firs t-line treatment of metastatic colorectal cancer (CRC) patients. 73 advance d CRC patients were randomised to receive either oxaliplatin 85 mg/m(2) eve ry 2 weeks (35 patients), or the same treatment combined with 5-FU 425 mg/m (2)/day and FA 20 mg/m(2)/day x 5 days every 4 weeks (38 patients). Treatme nt was continued until disease progression or unacceptable toxicity. All pa tients had documented inoperable disease and no previous chemotherapy for a dvanced disease. Based on the investigators' assessment of best response, o bjective response rate was 9% (95% confidence interval (CI) 2-24%) in the o xaliplatin arm, and 45% (95% CI 27-64%) in the oxaliplatin + 5-FU/FA arm. M edian progression-free survival(PFS) was 2 months (95% CI 1.7-2.4 months) i n the oxaliplatin arm and 3.9 months (95% CI 2.9-5 months) in the oxaliplat in + 5-FU/FA arm. Severe neutropenia was seen in 23% of patients in the oxa liplatin + 5-FU/FA arm, and none in the oxaliplatin arm. There were two tre atment-related deaths, both in the oxaliplatin + 5-FU/FA arm. In the oxalip latin + 5-FU/FA arm, severe diarrhoea, vomiting and stomatitis were seen in 34, 14 and 14% of the patients, respectively. In conclusion, oxaliplatin a t a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limit ed activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day + FA 20 mg/m (2)/day x 5 days every 4 weeks), although active, was unfeasible due to a h igh level of myelosuppression and gastrointestinal toxicity. Alternative lo wer dosing or other regimens are to be explored to ascertain the value of b olus 5-FU/FA combined with oxaliplatin. (C) 2001 Published by Elsevier Scie nce Ltd. All rights reserved.