Platinum organ toxicity and possible prevention in patients with testicular cancer

Advances in the management of metastatic testicular cancer are attributed mainly to the introduction of cisplatin into combination chemotherapy. In parallel with the development of effective chemotherapy resulting in long-term survival for the majority of patients, possible adverse effects of treatment have been systematically investigated. Besides acute side effects of cisplatin, such as gastro-intestinal toxic effects and moderate myelosuppression, reduction in glomerular filtration rate occurs in 20% to 30% of patients despite prophylactic intensive hydration and forced diuresis. Such changes in glomerular function are essentially irreversible. Persistent effects on tubular renal function occur less commonly, but hypomagnesemia due to hypermagnesiuria is often seen. Neurotoxicity, mainly sensory peripheral neuropathy, is common during treatment but disappears in the majority of patients after its completion. However, persistent paresthesias are found in 20% to 60% of patients. A typical audiometric abnormality affecting up to 50% of patients is bilateral loss of hearing at 4 to 8 kHz. A correlation between the cumulative cisplatin dose applied and the frequency of neuro- and nephrotoxicity has been demonstrated in some studies. The administration schedule additionally appears to influence the extent of toxicity, whereby single-day infusion schedules are associated with pronounced neural and renal toxicity, possibly due to higher peak plasma levels of cisplatin. Other long-term abnormalities after treatment with cisplatin-based combination regimens are a weak predisposition to secondary malignancies, infertility and chronic vascular toxicity. Several strategies have been developed to reduce such side effects. Ongoing trials are investigating the role of the aminothiol amifostine as a nephro- and neuroprotectant.