Chemotherapy-Induced Malignancies in Rats after Treatment with Cisplatin as Single Agent and in Combination: Preliminary Results

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Abstract
6 groups of 24–50 BD IX rats, each, were treated with cis-diamminedichloroplatinum (CDDP)-(II) alone or in combination chemotherapy. The animals were either bearing transplanted adenocarcinomas of the stomach or large bowel, or were treated without having any tumors, to study the long-term consequences of the chemotherapy. CDDP was given within 3 weeks either as 9 × 1 mg/kg body weight, or 9 × 2 mg/kg. Autopsy findings revealed fibrosarcomas of the kidneys and/or leukemias in each of the six groups, while the 77 animals of the control group, which did not receive chemotherapeutic agents, did not show any malignancies in postmortem examinations. In one group of rats, which received CDDP in combination with 1-methyl-1-nitroso-urea (MNU), 50% of the animals that survived chemotherapy for more than 100 days died of malignancies, mainly of fibrosarcomas of the kidneys and leukemias. In another group, 24% of the animals, which survived more than 100 days after chemotherapy with CDDP alone, had developed myeloic leukemias. We therefore may presume that a carcinogenic risk in cancer chemotherapy with CDDP is also present in humans.