CONTINUOUS-INFUSION OF 5-FLUOROURACIL BY DOUBLE ROUTE (INTRAVENOUS AND INTRAPERITONEAL) WITH MODULATION BY FOLINIC ACID - CLINICAL AND PHARMACOKINETIC, PHASE-I STUDY IN PATIENTS WITH INTRAABDOMINAL MALIGNANCIES

Thirteen patients with intra-abdominal malignancies entered a phase I study of fluorouracil (5-FU) given by continuous infusion (96 h) iv an d ip, simultaneously, and modulated by high-dose folinic acid-iv. Seve re but reversible stomatitis was the only dose-limiting toxicity at a dose of 5-FU of 550 mg/m2/day. Local toxicity (5-FU-induced abdominal pain) was a significant side effect in patients receiving more than 1 cycle. The pharmacokinetic advantage of 5-FU-ip was confirmed in our s tudy (ratio AUC peritoneum/plasma between 160 and 328). The systemic e xposure to 5-FU (plasmatic AUC ranging from 73.4 to 173.21 muM) and to AF were found in efficacious ranges. The recommended dose of 5-FU iv and ip is 500 mg/m2/day. This regimen is feasible and may potentially have application for adjuvant chemotherapeutic programs after surgery for colorectal cancer.