A weekly 24-h infusion of high-dose 5-fluorouracil (5-FU)+leucovorin and bi-weekly cisplatin (CDDP) was active and well tolerated in patients with non-colon digestive carcinomas

In patients with non-colon digestive carcinomas, various schedules and dose s of 5-fluorouracil (5-FU) and leucovorin combined with cisplatin (CDDP) ha ve been used extensively. The present study explored the toxicity and activ ity of a weekly 24-h infusion of high dose 5-FU modulated by high dose leuc ovorin with bi-weekly CDDP. 59 patients with measurable disease were treate d with a weekly infusion of high dose 5-FU (2 or 2.6 g/m(2))+leucovorin 500 mg/m(2) for 6 weeks and a bi-weekly dose of CDDP (50 mg/m(2)). All patient s had metastatic or locoregionally advanced disease and had a performance s tatus less than or equal to3. All patients were evaluable for toxicity and 58 for response. Toxicity was different according to the schedule of 5-FU. Serious adverse events occurred most frequently when 5-FU was given at a do se of 2.6 g/m(2) with a high incidence of grade 3/4 neutropenia (16%) and f ebrile neutropenia (13%), and led to dose reductions in both CDDP and 5-FU in 13 patients (34%). For patients who started 5-FU at a dose of 2 g/m(2), no reduction in 5-FU was required, and only 4 patients required a dose redu ction of CDDP (19%). Grade 3/4 neutropenia was seen in 10% of patients of t his group and only 1 patient required hospitalisation for febrile neutropen ia. Other grade 3/4 toxicities were rare in both groups. Renal toxicity was infrequent and mild and did not require dose adjustments. The overall resp onse rate was 33%; 19 patients achieved a partial responses (PR). No patien t had a complete response (CR). The median duration of response was 5.7 mon ths (range 2-24 months) and the median survival was 7.9 months ( range: 1-3 0, 95% confidence interval (CI): 7-9). The combination of weekly 24-h infus ion of high dose 5-FU with leucovorin and bi-weekly cisplatin seems a well- tolerated and active treatment in non-colon digestive carcinomas. A dose of 2 g/m(2) of 5-FU seems to be recommended. (C) 2001 Elsevier Science Ltd. A ll rights reserved.