Phase-I Study of Protracted Infusion of Cisplatin

Abstract

A continuous infusion schedule for cisplatin employing a portable infusion pump was studied in a phase-I trial designed to establish an optimal daily dose rate to deliver drug for protracted periods (up to 30 days). Fifteen trials were carried out in 14 patients at daily dose rates of 5, 6.5, 7.5, and 10.0 mg/M2 X day. The median duration of therapy at the respective doses was 21, 17, 8, and 7 days. Dose-limiting toxicity was recalcitrant and protracted nausea was observed in all patients receiving greater than 5 mg/M2 X day. One patient did develop mild thrombocytopenia (98,000) at day 35. Renal failure was relatively minor considering the absence of a concomitantly delivered hydration regimen but 3 patients did develop a transient rise in serum creatinine, 2 of whom had a solitary kidney or partial urinary tract obstruction. No patient developed renal failure at 5 mg/M2 X day. At the recommended dose of 5 mg/M2 X day, the cumulative dose of cisplatin delivered by a protracted infusion schedule is comparable to the intermittent high-dose regimen with less adverse drug complications.