Chovanec M, Abu Zaid M, Hanna N, El-Kouri N, Einhorn L H, Albany C
Division of Hematology Oncology, Indiana University Simon Cancer Center, Indianapolis, USA;; 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia;; National Cancer Institute, Bratislava, Slovakia.
Division of Hematology Oncology, Indiana University Simon Cancer Center, Indianapolis, USA.
Ann Oncol. 2017 Nov 1;28(11):2670-2679. doi: 10.1093/annonc/mdx360.
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 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.
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.
GCT survivors cured with cisplatin-based chemotherapy are at risk for long-term side-effects. Detection of single-nucleotide polymorphisms 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.
睾丸生殖细胞肿瘤（GCT）具有很高的治愈率。多学科方法，包括基于顺铂的化疗，已使大多数GCT患者得以治愈。因此，幸存者的预期寿命将在确诊后延长数十年。与基于顺铂的化疗相关的晚期治疗毒性可能会影响他们未来的健康。
系统评价有关顺铂对GCT幸存者长期毒性的证据。
我们于2017年2月根据系统评价和Meta分析的首选报告项目（PRISMA）声明对PubMed/Medline进行了严格审查。根据报告试验的统一标准（CONSORT）标准对确定的报告进行了审查。选择了83篇出版物纳入本分析。
纳入的报告评估了基于顺铂的化疗对GCT幸存者的长期毒性。发现了报告神经毒性和耳毒性、继发性恶性肿瘤、心血管、肾脏和肺部毒性、性腺功能减退和不育的研究。七项研究（8%）报告了长期毒性的遗传基础，三项研究（4%）和十四项研究（19%）分别将长期毒性与循环铂水平和顺铂累积剂量相关联。报告了与顺铂和基于铂的方案相关的长期毒性的重大风险。顺铂累积剂量和循环铂被报告为风险因素。与野生型个体相比，几种单核苷酸多态性确定了对顺铂敏感的患者。
接受基于顺铂化疗治愈的GCT幸存者存在长期副作用的风险。单核苷酸多态性的检测可能是预测长期毒性的有价值工具。
本文总结了基于顺铂的化疗对GCT幸存者长期毒性的现有证据，并提供了印第安纳大学的见解。
