Diaziquone given as a bolus has not been effective in patients with relapsed or refractory
leukemia. Because of in vitro data suggesting enhancement of
diaziquone-induced cytotoxicity for human and murine
leukemia cells with increased duration of
drug exposure and the relatively short terminal plasma half-life of
diaziquone, 49 patients (34
acute nonlymphocytic leukemia [
ANLL], six
chronic myelogenous leukemia in
blast crisis [CML-B], five
acute lymphocytic leukemia [ALL], four 2 degrees
ANLL) with
leukemia were given
diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed
ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL.
Thrombocytopenia in these patients was felt to be a manifestation of
diaziquone effect, not persistence of
leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS
leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease.
Diaziquone produced prolonged aplasia in patients with secondary
ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of
leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed
ANLL render
diaziquone of interest as second-line
therapy or consolidation
therapy in first remission for patients with
ANLL.