Carcinogenic effect of cisplatin (cis-diammine-dichloroplatinum (II), CDDP) in BD IX rats

The potent antitumor agent cis-diammine-dichloroplatinum(II) (CDDP) also has carcinogenic properties. CDDP was administered i.p. to 50 BD IX rats for 3 weeks, 3 X 1 mg/kg body weight per week. All animals were pretreated by hydration before each CDDP application, but only half the animals additionally received mannitol together with the CDDP solution, as a nephroprotective measure. To date, 455 days after the first application, 33 animals have died, 13 of them of malignancies: 12 leukemias and 1 renal fibrosarcoma. So far, no significant differences in the frequency and type of malignancies have been observed between animals which additionally received mannitol and the others which did not. In the control group of 25 animals, which received NaCl solution 0.9% i.p. (3 X 1 ml/kg per week, for 3 weeks) malignancies have not yet occurred. The high tumor incidence determined in this study reveals that the risk of secondary tumor development in patients treated with CDDP should not be disregarded.