Platinum organ toxicity and possible prevention in patients with testicular cancer

Advances in the management of metastatic testicular cancer are attributed m ainly to the introduction of cisplatin into combination chemotherapy. In pa rallel with the development of effective chemotherapy resulting in long-ter m survival for the majority of patients, possible adverse effects of treatm ent have been systematically investigated. Besides acute side effects of ci splatin, such as gastro-intestinal toxic effects and moderate myelosuppress ion, reduction in glomerular filtration rate occurs in 20% to 30% of patien ts despite prophylactic intensive hydration and forced diuresis. Such chang es in glomerular function are essentially irreversible. Persistent effects on tubular renal function occur less commonly, but hypomagnesemia due to hy permagnesiuria is often seen. Neurotoxicity, mainly sensory peripheral neur opathy, Is common during treatment but disappears in the majority of patien ts after its completion. However, persistent paresthesias are found in 20% to 60% of patients. A typical audiometric abnormality affecting up to 50% o f patients is bilateral loss of hearing at 4 to 8 kHz. A correlation betwee n the cumulative cisplatin dose applied and the frequency of neuro- and nep hrotoxicity has been demonstrated in some studies. The administration sched ule additionally appears to influence the extent of toxicity, whereby singl e-day infusion schedules are associated with pronounced neural and renal to xicity, possibly due to higher peak plasma levels of cisplatin. Other long- term abnormalities after treatment with cisplatin-based combination regimen s are a weak predisposition to secondary malignancies, infertility and chro nic vascular toxicity. Several strategies have been developed to reduce suc h side effects. Ongoing trials are investigating the role of the aminothiol amifostine as a nephro- and neuroprotectant. (C) 1999 Wiley-Liss, Inc.