Phase I study of protracted venous infusion of 5-fluorouracil.

A Phase I study of protracted continuous infusion 5-fluorouracil was undertaken at a starting dose of 200 mg/m2/day. The drug was delivered via a tunneled subclavian venous access site by a portable infusion pump (Cor-Med) permitting ambulatory monitoring. Seventeen patients were administered 19 courses at incremental dose rates from 200 mg/m2/day to 600 mg/m2/day; treatment was terminated at the onset of stomatitis. At dose rates of 300 mg/m2/day or less, the treatment did not require interruption for up to 60 days or up to 36 g cumulative dose. For dose rates of 350 to 600 mg/m2/day, the treatment always required interruption: mean duration 20 day for 350 mg/m2/day; 9 day for 400 mg/m2/day; and 14 day for 600 mg/m2/day. Mean cumulative dose at the higher dose rates was 10.9 g (350 mg/m2/day); 7.9 g (400 mg/m2/day); and 15.3 g (600 mg/m2/day). Mean cumulative dose at 200 mg/m2/day was 11.5 g and at 300 mg/m2/day, was 22.6 g. Protracted venous infusion allows for a substantial cumulative dose of 5-FU and at dose rate delivery of 300 mg/m2/day may be administered for up to 60 days without adverse effects due to the drug or to the presence of an indwelling venous access line.