GEMCITABINE (dFdC), 5-FLUROURACIL (5FU), AND FOLINIC ACID (FA) IN THE TREATMENT OF PATIENTS WITH GASTRO-ENTERIC CARCINOMAS: A CLINICAL AND PHARMACOLOGICAL STUDY.

Purpose. To perform a phase I clinical study of a combination therapy based on the Tomudex-PVI-5-FU sequence. Patients and Methods: From 07/07/97 to 15/10/99, 15 patients with ileal or colorectal cancer received 62 courses (6 planned for every patient, consisting of 2 weeks therapy followed by 1 week rest) of Tomudex (given as a single 15-nunule intravenous infusion every 3 weeks, at escalating doses from 2 to 3 mg/m2) followed by PVI-5-FU (given as a 14 days infusion every 3 weeks, at escalating doses from 200 to 300 mg/m2/die). There were 10 men and 5 women with a median age of 64 years (range, 40 to 77). Eleven patients (84,6%) had previously received chemotherapy (PVI-5-FU, FudR hepatic arterial infusion. Stop-flow, intraoperative peritoneal chemohyperthermia) for advanced malignancy. Results: only 7 courses were discontinued (3 because of biliary stent obstruction in the same patient, 1 owing to erythema, 1 because of arrhythmia, 1 because of subcutaneous port pocket infection and the last owing to personal reasons) No side effects >WH0 2° were seen, with the exception of asymptomatic rise in AST-ALT (WHO 3° in 2 courses and 4° in 1 course, in the same patient), nausea and vomiting (WHO 3° in 1 course, WHO 4° in 1 course), mucositis (WHO 4° in 1 course, after that dose reduction was required) and diarrhoea (WHO 4° in 2 course; dose reduction was required in 1 patient) Dose reductions due to toxicity were required in 2 patients (at 5-FU 300 mg/m2 step); delayed courses in 6 cases. Haematological side effects (Leucopenia WHO 1° in 1 course and WHO 2° in 1 course, anaemia WHO 1° in 7 courses), other gastrointestinal side effects (diarrhoea WHO 1° in 4 courses and WHO 2° in 8 courses, nausea and vomiting WHO 1 ° in 11 courses, WHO 2° in 1 course and WHO 3° in 1 course), mucositis (WHO 1° in 1 course and WHO 2° in 1 course) and skin erythema (WHO 1° m 6 courses and WHO 2° in 2 courses) were mild and easy manageable. Among 12 patients evaluable after 3 courses there were PR 2, MR 1, SD 6, PD 3. 6 patients are evaluable after 6 courses and we found . PR 1, MR 1, SD 1, PD 3. Conclusions The combination of TOM + PVI-5-FU is well tolerated DLT is gastrointestinal toxicity (nausea and vomiting, diarrhoea) and mucositis MTD has been established: Tomudex 3 mg/m2 and 5-FU 250 mg/m2 Clinical activity looks encouraging. Further Phase II is planned