Oxaliplatinum and 5-fluorouracil in protracted infusion in the treatment of advanced colorectal cancer

Aim. Oxaliplatinum (OHP) and 5-fluorouracil (5FU) are active drugs in metastatic colorectal carcinoma (CRC); laboratory and clinical studies suggest a synergic interaction between the two agents. This phase II study was performed to evaluate the activity and the tolerance of a schedule including OHP and 5FU protracted infusion (pi), in 5FU-resistant advanced CRC. Patients and methods. From October 1997 to January 2000, 50 patients with measurable metastatic CRC, in progression after one or more 5FU-based regimens, were treated. Both drugs were employed at 2 dose levels (OHP 100 and 130 mg/m2, 5FU 200 and 250 mg/m2/day) and administered every 3 weeks (OHP in 3 hours intravenous infusion on day 1 and 5FU pi on days 1-21). Results. One (2%) complete response, 10 (20%) partial responses and 23 (46%) stable diseases were observed. The higher number of objective responses was obtained with the higher dose regimen and in the patients who had previously received no more than one line of chemotherapy. The median time to progression was 4 months (1-9). All dose levels (313 cycles) were well tolerated with mild toxicity. Major toxicity (grade 3 WHO) included: anaemia in one patient (2%), nausea and vomiting in one patient (2%), diarrhoea in 4 patients (8%) and stomatitis in one patient (2%); grade 1 and 2 peripheral neuropathy were encountered respectively in 30 (60%) and 8 (16%) patients. The median survival was 13 months, with 32 patients still alive after a median follow-up of 8 months. Conclusions. This study suggests that OHP/5FU pi is an active combination in metastatic CRC patients pretreated with 5FU. This regimen has an acceptable toxicity profile and the optimal dose level is OHP 130 mg/m2 and 5FU 250 mg/m2.