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.
Fifty chemotherapy trials with 5‐fluorouracil;31 mitomycin C;9 vinblastine;3 Adriamycin;5 and cis‐platinol2 were initiated employing constant (24‐hour) intravenous infusion for protracted periods (14–94 days). The use of the tunneled subclavian line for greater than 2200 patient days was associated with minimal complications and no instances of thrombosis or infection were observed. The use of an ambulatory infusion pump was associated with a pump efficiency of greater than 85% in 38 of 39 evaluable trials. Only four of 50 trials were associated with excess drug infusion and in no instance was a drug complication encountered. Constant infusion cancer chemotherapy is feasible, reliable, and safe. Objective tumor regression is observed but the superiority of this drug schedule over the standard intermittent bolus schedule is yet to be determined. Nonetheless, drug toxicity patterns are altered substantially and, in particular, gastrointestinal side effects of chemotherapeutic drugs may be eliminated without compromising cumulative dose.
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