Haematological toxicity of carboplatin in rats

In rats a maximal tolerated dose of carboplatin (60 mg kg-1, i.v.) caused severe anaemia, leucopenia and thrombocytopenia. These indices of haematological toxicity were also observed with a maximal tolerated dose of cis-platin (6.5 mg kg-1, i.v.), but reductions in blood cell counts were less than those observed with carboplatin. Anaemia was deduced to be the dose-limiting toxicity of carboplatin, since red cell transfusions afforded protection to rats receiving a lethal dose of this compound (80 mg kg-1, i.v.). Anaemia did not appear to be due to an increase in the susceptibility of cis-platin- or carboplatin-exposed red cells to lysis, as concluded from results of osmotic fragility tests. These red cells, when tagged with 51Cr, also did not exhibit reductions in survival time. Administration of 51Cr-labelled control red cells to rats, which had been treated with carboplatin 3 days earlier, resulted in substantial loss of the radiolabel from the circulation, indicating that internal haemorrhaging, as a result of thrombocytopenia, is probably the principle cause of drug-induced anaemia.