Progress in the development of childhood cancer therapy

Despite the continuous improvement of cancer treatment protocols, altered testicular function and infertility frequently represent major adverse effects of oncologic treatments. Thus, strong efforts are needed to avoid or at least to reduce these complications that are particularly relevant in young men without offspring. Furthermore in the last years, concerns have been raised about the possible mutagenic effect of chemotherapy on sperm. Alkylating agents are frequently and successfully used in the treatment of paediatric tumors despite their well-known gonadotoxic effect. While gonadal toxicity of cyclophosphamide has been well demonstrated, little and conflicting data are reported about the effects on testicular function of ifosfamide. The aim of this study was to compare long-term effects of ifosfamide versus cyclophosphamide based therapies, on testicular function, fertility and sperm aneuploidies in a group of 33 young males survivors of childhood cancer. Patients who had received cyclophosphamide showed a severe gonadal failure characterized by reduced testicular size, very low sperm count and some degree of Leydig cell impairment. On the contrary, in subjects who had received ifosfamide all parameters of testicular function including sperm aneuploidies were in the normal range, despite of different dose, protocol of infusion and pubertal stage at treatment. In conclusion, our results confirm data of literature reporting the high gonadal toxicity of cyclophosphamide and suggest that ifosfamide treatment seems to be safer for testicular function and fertility.