A phase I trial of carboplatin and etoposide given as continuous infusions to adults with leukemia

Thirty-two adult patients with acute leukemia were treated with continuous infusion carboplatin and etoposide at eight different dose levels. Dose limiting toxicity was encountered at doses of carboplatin of 310 mg/m2 per day for 5 days (total 1550 mg/m2 per course) and etoposide 150 mg/m2 per day for 5 days (total dose 750 mg/m2 per course) and consisted primarily of gastrointestinal toxicity. Of the five courses given at the highest dose level, three were complicated by grade 4 gastrointestinal toxicity. The recommended dose for further phase II evaluations in acute leukemia is carboplatin 250 mg/m2 per day for 5 days by continuous infusion and etoposide 150 mg/m2 per day for 5 days given by continuous infusion. The response to treatment was notable for a single complete remission achieved in a patient with acute undifferentiated leukemia. None of the patients with chronic myeloid leukemia in blast crisis (n = 12) or with acute lymphocytic leukemia (n = 4) or acute myeloid leukemia (AML) (n = 15) achieved complete remission (CR), although all patients with AML entered on this trial had prior complete remissions that were less than 1 year in duration, and many were refractory, either to primary therapy or to the most recent attempt to obtain CR.