HEMATOLOGICAL TOXICITY OF CARBOPLATIN AND CISPLATIN COMBINED WITH WHOLE-BODY HYPERTHERMIA IN RATS

Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplat inum (II) (cisplatin) in combination with whole body hyperthermia (WBH ) (2 h at 41.5-degrees-C) was examined using a F344 rat model. The the rmal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anae mia and leukopenia were determined from the dose-response curves of th e nadir values of the peripheral platelet, RBC and WBC counts. Carbopl atin produced profound depression of platelet counts which was over th ree-fold greater than cisplatin (14% vs 51% of the control), while the decrease in WBC and RBC counts induced by carboplatin did not differ significantly from those observed with cisplatin. These carboplatin or cisplatin-mediated haematological toxicities were significantly enhan ced by WBH. The depth of decrease in platelet, RBC and WBC counts indu ced by the maximum tolerated dose (MTD) of carboplatin (30 mg kg-1) co mbined with WBH was identical to that induced by the MTD of carboplati n (70 mg kg-1) alone. The TERs of carboplatin-mediated thrombocytopeni a, anaemia and leukopenia were 2.0, 2.8 and 1.9, respectively. The the rmal enhancement of cisplatin mediated haematological toxicity was sim ilar to that of carboplatin, with TERs of 1.8 for thrombocytopenia, 2. 4 for anaemia and 1.9 for leukopenia. These data, demonstrating therma l enhancement of cisplatin or carboplatin-mediated haematological toxi city, must be taken into account in the clinical application of the co mbination thereapy of platinum and WBH.