Hyperthermic Enhancement of cis-Diammine-1,1-cyclobutane Dicarboxylate Platinum(II) Cytotoxicity in Human Leukemia Cells in Vitro1

Hyperthermic enhancement of cis-diammine-l,l-cyclobutane dicarboxylate platinum(II) (carboplatin) cytotoxicity was studied in vitro in .IM, a human acute lyntphoblastic leukemia cell line. Corrected for direct heat toxicity, hyperthermia enhanced carboplatin killing at the clinically relevant temperatures of 40.5°and 41.8°C.The thermal enhancement ratios at these temperatures were 1.89 and 332, respectively. Cell killing increased exponentially with increasing duration of combined treatment (41.8°C, carboplatin 30 «tg/ml) for at least 3.5 h. Hyperthermic enhance ment was maximal when heat was given during or immediately before carboplatin; enhancement was diminished when heat preceded carbopla tin by more than an hour and was not apparent when heat followed drug treatment. As carboplatin is associated with different clinical toxicity than is cisdiamminedichloroplatinum(II), carboplatin may represent an ideal drug in its class of anticancer agents to use in clinical whole body hyperthermia trials.