Long-term toxicity of cisplatin in germ-cell tumor survivors

Abstract

Context: 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. Objective: To systematically evaluate evidence regarding the long-term toxicity of cisplatin in GCT survivors. Evidence acquisition: We carried out 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. Evidence synthesis: 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 identified patients susceptible to cisplatin compared with wild-type individuals. Conclusions: GCT survivors cured with cisplatin-based chemotherapy are at risk for long-term side-effects. Detection of singlenucleotide polymorphisms could be a valuable tool for predicting long-term toxicities. Patient summary: Herein, this article summarizes the available evidence of long-term toxicity of cisplatin-based chemotherapy in GCT survivors and provide insights from Indiana University.