Combination of Hematopoietic Growth Factors Granulocyte-Macrophage Colony-Stimulating Factor, Interleukin-1 Reduces Toxicity of Cisplatin, Carboplatin, and Azidothymidine on Normal Human and Murine Hematopoietic Progenitors

Myelodepressive activity is the main limiting toxicity of most anticancer and of many antiviral drugs. Their combination with hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, GM-CSF; interleukin-1 IL-1) appears to be a possible means for reducing this myelotoxicity and enhancing the therapeutic index of these drugs. An expanding body of experimental and clinical research is now pursuing this goal. Our purpose was to test the effects of a combination of two major cytokines, IL-1 and GM-CSF, on the toxicity of cisplatin (DDP) and its analogue carboplatin (CBDCA) and of the antiviral drug azidothymidine (AZT) on murine and human hematopoietic progenitors cultured in vitro. With proper hydration and diuresis, myelosuppression is the dose-limiting toxicity of DDP [1], which is today an important feature in the treatment of several human cancers. CBDCA is relatively free of nephrotoxicity and neurotoxicity, but it shows a rather severe depressive activity on myelopoiesis [2]. AZT, a synthetic thymidine analogue, is currently used in the treatment of acquired immunodeficiency syndrome. AZT induces myelosuppression involving all hematopoietic cell lines from the progenitor phase to the later steps of differentiation and maturation [3, 4].