Procarbazine and infertility in low-grade gliomas in children.

TO THE EDITOR: We read with interest the publication by Ater et al on the comparison between two different chemotherapy regimens for low-grade glioma in children. The primary aim was to compare the event-free survival but the stated secondary aims included a comparison of toxicity of the two regimens. The discussion mentions the fear that the TPCV (thioguanine, procarbazine, CCNU, vincristine) regimen may increase the risk of secondary neoplasms however there is no mention of the risk of infertility from procarbazine in TPCV. The protocol includes procarbazine 200 mg/m/cycle for a total of eight cycles giving a cumulative dose of 1,600 mg/m. The TPCV protocol was based on the TPDCV (thioguanine, procarbazine, dibromodulcitol, CCNU, vincristine) regimen with the exclusion of the dibromodulcitol but even a recent publication on 15 years follow-up of pediatric patients with low-grade hypothalamic/chiasmatic glioma treated with this regimen makes no mention of fertility or folliclestimulating hormone measurements. It is well known from the literature on Hodgkin lymphoma in children that there is a relationship between the cumulative doses of gonadotoxic drugs, especially procarbazine, and the extent of testicular damage and the azoo/hypospermia is usually irreversible. With an overall survival for low-grade gliomas of 85% and the likelihood that the majority of these patients will reach adulthood, lasting testicular damage with severely impaired spermatogenesis could be particularly distressing to the many young adults cured of their glioma. In addition, the vast majority of these patients will be too young for fertility preservation techniques such as sperm banking. This issue needs to be addressed in the decision making process regarding treatment options together with the family of a child with a low-grade glioma and should be documented in long-term follow-up studies of TPCV and similar procarbazine-containing regimens. Considering the morbidity of gonadal dysfunction, efforts are needed to test alternative treatment regimens with less gonadotoxic chemotherapeutic agents or hopefully new biologic targeted therapies for low-grade gliomas in children.