Long-Term Toxicity of Cisplatin in Germ-Cell Tumor Survivors

Testicular germ cell tumors (GCT) are highly curable. A multidisciplinary approach, including cisplatin-based chemotherapy has resulted in cure in the majority of patients with GCT. Thus, the life expectancy of survivors will extend to many decades post diagnosis. Late treatment toxicities associated with cisplatin-based chemotherapy may impact their future health.

To systematically evaluate evidence regarding the long-term toxicity of cisplatin in GCT survivors.

We performed a critical review of PubMed/Medline in February 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Identified reports were reviewed according to the Consolidated Standards of Reporting Trials (CONSORT) criteria. Eighty three publications were selected for inclusion in this analysis.

Included reports evaluated long-term toxicities of cisplatin-based chemotherapy in GCT survivors. Studies reporting neuro- and ototoxicity, secondary malignancies, cardiovascular, renal and pulmonary toxicities, hypogonadism and infertility were found. Seven studies (8%) reported genetic underpinnings of long-term toxicities and 3 (4%) and 14 (19%) studies correlated long-term toxicities with circulating platinum levels and cumulative dose of cisplatin, respectively. Significant risks for long-term toxicities associated with cisplatin and platinum-based regimens were reported. The cumulative dose of cisplatin and circulating platinum were reported as risk factors. Several single-nucleotide polymorphisms (SNPs) identified patients susceptible to cisplatin compared to wild-type individuals.

GCT survivors cured with cisplatin-based chemotherapy are at risk for long-term side effects. Detection of SNPs could be a valuable tool for predicting long-term toxicities.

Herein, this article summarizes the available evidence of long-term toxicity of cisplatin-based chemotherapy in GCT survivors and provide insights from Indiana University.

Annals of oncology : official journal of the European Society for Medical Oncology. 2017 Jul 14 [Epub ahead of print]

M Chovanec, M Abu Zaid, N Hanna, N El-Kouri, L H Einhorn, C Albany

Division of Hematology Oncology, Indiana University Simon Cancer Center, Indianapolis, IN, USA., 2nd Department of Oncology, Faculty of Medicine, Comenius University and National Cancer Institute, Bratislava, Slovakia.