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Interactions of Thymidine, Hyperthermia, and cis-Diammine-1,1-cyclobutane Dicarboxylate Platinum(II) in Human T-Cell Leukemia¹

University of Wisconsin Clinical Cancer Center, Madison, Wisconsin 53792

Using JM and MOLT3, two human T-cell acute lymphoblastic leukemia cell lines, we investigated the ability of 24-h thymidine exposures to enhance the cytotoxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) (carboplatin). Clinically achievable thymidine concentrations (for 24 h) significantly enhanced carboplatin killing. Unexpectedly, thymidine-carboplatin enhancement was as great at a relatively low 200-µg thymidine/ml as at the clinically much more toxic range of 1000 µg/ml. For a constant thymidine concentration (500 µg/ml), thymidine-carboplatin interaction increased with longer thymidine exposures until about 16 to 24 h. Thymidine and 41.8°C hyperthermia (for 1 h) together enhanced carboplatin killing significantly more than did hyperthermia-carboplatin or thymidine-carboplatin combinations. These results show that relatively brief, presumptively nonmyelosuppressive thymidine exposures can significantly increase carboplatin killing. Carboplatin-thymidine killing can then be further augmented by 41.8°C hyperthermia.

¹ Supported by Midwest Athletes Against Childhood Cancer, Inc.; The Thorton Fund for Neurooncology Research; and NIH Grant R01 CA 35464.

² Supported by NIH Physician Scientist Training Grant T32 CA 09614. To whom requests for reprints should be addressed, at University of Wisconsin Clinical Cancer Center, 600 Highland Ave., Madison, WI 53792.

Received 2/27/89. Revised 6/26/89. Accepted 7/27/89.

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