Dose-dependent impairment of testicular function in patients treated with cisplatin-based chemotherapy for germ cell cancer

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Abstract
The enormous differences in semen quality following cisplatin-based combination chemotherapy reported in previous studies may be caused by differences in the cisplatin dosages. We examined thirty-three patients treated with conventional-dose PEB (cisplatin 20 mg/m2 × 5, q3w, etoposide 100 mg/m2 × 5 q3w and bleomycin 15 mg/m2 q1w) and 21 patients treated with high-dose PEB (cisplatin 40 mg/m2 × 5 q3w, etoposide 200 mg/m2 × 5 q3w and bleomycin 15 mg/m2 qlw). The sperm density was significantly higher (median 5.83 mill/ml) in the conventionally-treated group than in the group of high-dose-treated patients (median 0.005 mill/ml) (p = 0.008). Azoospermia was present in 19% of the conventionally- and in 47% of the high-dose-treated patients. All patients treated with a cumulative cisplatin dose above 600 mg/m2 had severe oligospermia or azoospermia. Serum values of basal follicle-stimulating hormone (FSH) (median 27.2 iu/l vs. 15.2 iu/l) and stimulated FSH (median 57.7 iu/l vs. 28.4 iu/l) were significantly higher in the high-dose group than in the conventionally-treated group. No differences could be detected in basal or stimulated testosterone or in luteinizing hormone in serum. In patients treated with PEB for testicular cancer, we found strong evidence that the impairment of spermatogenesis is dose-dependent.