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The anthracycline antibiotics daunomycin and 14-hydroxydaunomycin (adriamycin) have been shown to be very effective in the treatment of a number of malignancies (1). Besides the non-specific side-effects of cytostatic agents, adriamycin exerts a specific toxic activity on the heart (2). This side effect may eventually lead to a life-threatening congestive heart failure when a cumulative dose of 550 mg.m-2 has been exceeded. Although the exact mechanism through which toxicity develops has not been elucidated, three major hypotheses on the pathogenesis of adriamycin induced cardiotoxicity have been postulated. As all quinones, adriamycin is a potent chelating agent for divalent cations, in particular for Ca2+ which is involved in the excitation-contraction coupling of muscle cells (3). Adriamycin can be converted to a semi-quinone either by microsomal or by mitochondrial metabolic pathways. These semiquinones give rise to the formation of free radicals, which may lead to peroxidation of polyunsaturated fatty acid structures (4). Finally, adriamycin is a strong intercalating agent, which causes an inhibition of RNA, DNA protein synthesis. Inhibition of the synthesis of contractile proteins and of reparative growth (5) will lead to a gradual decline of contractile properties of the heart.

Cis-diamminodichloroplatinum II (cisplatin) is the first member of a group of platinum coordination complexes, which were shown to possess antitumor activity (1). With the introduction of cisplatin into the clinic the spectrum of tumors which can be treated effectively with chemotherapy has broadened (2). This agent is increasingly utilized in first-line regimens against testicular cancer, ovarian cancer, head and neck cancer, bladder cancer, while results in squamous cell cancer of the uterine cervix and in some childhood solid tumors like neuroblastoma and osteogenic sarcoma have been most promising. However, the use of the drug is hampered by some serious side effects. Its major clinical disadvantages are intense nausea and vomiting and renal impairment (3,4). Nausea and vomiting are much more distressing than found with other cytostatic drugs and cannot be effectively prevented. Adequate hydration and attention paid to optimal urinary flow results in a decrease in the incidence and the severity of nephrotoxicity. Nevertheless, substantial decrease in glomerular filtration rate and effective renal plasma flow can be found, which may be at least partially irreversible (5,6). Other toxicities include neurotoxicity, ototoxicity, myelosuppression, diarrhea and occasional liver function test abnormalities, electrolyte imbalances and occasional anaphylactic-like reactions (7). Although nephrotoxicity is generally considered as the major dose limiting toxicity, methods to overcome this toxicity have created the possibility to administer multiple courses of the drug. With prolonged treatment other toxicities may become dose-limiting. Recognition of these limitations has stimulated a widespread search for alternative platinum complexes with equal or greater antitumor activity but with decreased toxicities.