Oxaliplatin in combination with infusional 5-fluorouracil and leucovorin every 2 weeks as first-line treatment in patients with advanced colorectal cancer: A phase II study

Purpose: To evaluate the efficacy and safety of oxaliplatin (L-OHP) in comb ination with leucovorin (LV)-modulated bolus plus infusional 5-fluorouracil (5-FU; de Gramont schedule) every 2 weeks in chemotherapy-naive patients w ith advanced colorectal cancer (CRC). Patients and Methods: Thirty-two pati ents (median age: 69 years) with histologically confirmed and two-dimension ally measurable metastatic CRC were enrolled. The patients' performance sta tus (WHO) was 0 in 14 (44%), 1 in 15 (47%), and 2 in 3 (9%) patients. Twent y (62.5%) patients had at least two metastatic sites. LV was administered a t a dose of 200 mg/m(2)/day as a 2-hour intravenous infusion, followed by 5 -FU as an intravenous bolus at the dose of 400 mg/m(2) and then, as a 22-ho ur continuous infusion at the dose of 600 mg/m(2)/day for 2 consecutive day s. L-OHP was administered on day 1 at the dose of 85 mg/m(2) as a 2-hour in fusion in parallel with LV but using different infusion lines. Treatment wa s administered every 2 weeks. Results: In an intention-to-treat analysis, 2 (6.2%) complete and 9 (28%) partial responses (28%; odds ratio 34.2%; 95% confidence interval 17.92-50.83%) were achieved while 8 (25%) patients had stable disease and 13 (41%) progressive disease. The median duration of res ponse was 5 months, but the median time to progression has not yet been rea ched. After a median follow-up period of 11 months, the median survival has not yet been attained, but the projected probability for 1-year survival w as 72%. Grade 3/4 neutropenia occurred in 16 (50%) patients while 1 (3%) of them developed febrile neutropenia. There was no treatment-related death. Peripheral neuropathy grade 2 and greater than or equal to 3 occurred in 5 (16%) and 7 (21 %) patients, respectively. Conclusions: The bimonthly admin istration of L-OHP in association with LV-modulated bolus plus infusional 5 -FU ('de Gramont' regimen) is a well-tolerated and effective front-line tre atment for metastatic CRC. Copyright (C) 2001 S. Karger AG, Basel.