Infusional carboplatin. Phase I studies of 5-day and 14-day infusions

Twenty-two courses of carboplatin (Paraplatin; Bristol-Meyers, Evansville, IN) (CBDCA) were administered to 15 patients with advanced cancer on a continuous 24-hour per day infusion schedule for either 5 days or 14 days. The objective of the trial was to establish the optimal dose rate and cumulative dose for this treatment schedule. The dose-limiting toxicity was myelosuppression, with leukopenia and thrombocytopenia observed. The optimal dose rate for the 5-day infusion was 75 mg/m2/d or a total cumulative dose of 375 mg/m2/d. The optimal dose rate for the 14-day infusion was 25 mg/m2/d or a total cumulative dose of 350 mg/m2/d. The times to nadir levels of leukocyte and platelet counts were 34 days and 25 days, respectively, with a median time to recovery of 14 days and 7 days, respectively, in patients with Grade 3 or greater marrow suppression. The pattern of hematologic toxicity with infusional CBDCA is comparable to that seen with bolus schedules. There is, therefore, no clinical advantage of the infusional schedule for CBDCA in terms of toxicity and the dose delivered per cycle, and the dose intensity is slightly less than with a bolus schedule. If there is a therapeutic advantage for the infusional schedule, a prospective comparative trial against the standard bolus schedule will be required to establish it. Bolus and infusional schedules for CBDCA are associated with a delayed pattern of thrombocytopenia and prolonged leukopenia, necessitating 5 or more weeks between treatment cycles.