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

Department of Human Oncology, University of Wisconsin Clinical Cancer Center, University of Wisconsin Clinical Science Center, Madison, Wisconsin 53792

Hyperthermic enhancement of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin) cytotoxicity was studied in vitro in JM, a human acute lymphoblastic 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 3.32, respectively. Cell killing increased exponentially with increasing duration of combined treatment (41.8°C, carboplatin 30 µg/ml) for at least 3.5 h. Hyperthermic enhancement was maximal when heat was given during or immediately before carboplatin; enhancement was diminished when heat preceded carboplatin by more than an hour and was not apparent when heat followed drug treatment.

As carboplatin is associated with different clinical toxicity than is cis-diamminedichloroplatinum(II), carboplatin may represent an ideal drug in its class of anticancer agents to use in clinical whole body hyperthermia trials.

¹ Supported by Midwest Athletes Against Childhood Cancer.

² An American Cancer Society Clinical Oncology Fellow.

³ An American Cancer Society Fellow. Supported in part by Grant RO1-CA-35361. To whom requests for reprints should be addressed, at Department of Human Oncology, University of Wisconsin, Clinical Cancer Center, 600 Highland Avenue, Madison, WI 53792.

Received 2/ 6/87. Revised 5/21/87. Accepted 5/27/87.

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