Chaudhary Uzair B, Haldas Jason R
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Drugs. 2003;63(15):1565-77. doi: 10.2165/00003495-200363150-00004.
Testicular cancer is the most common solid tumour among young males aged 15-35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud's phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud's phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud's phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2-5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.
睾丸癌是15至35岁年轻男性中最常见的实体瘤。以顺铂为基础的联合化疗改变了这种疾病的预后。播散性睾丸癌曾经无一例外都是致命的，而现在联合化疗的治愈率超过了80%。系统性随机试验表明，顺铂、依托泊苷和博来霉素（PEB）联合化疗仍然是主要的治疗方法。虽然这种疾病患者化疗的治愈率很高，但现在已经认识到化疗会带来一些长期并发症，包括继发性白血病、治疗相关实体瘤、肾毒性、神经毒性、肺毒性、血管毒性和不育。依托泊苷是一种DNA拓扑异构酶II抑制剂，是发生白血病的一个重要危险因素；风险似乎与给药的总剂量相关。接受以顺铂为基础的联合化疗治疗睾丸癌的患者发生第二种非生殖细胞恶性肿瘤的相对风险似乎也更高；放疗加化疗联合治疗时，治疗相关实体瘤的风险最大。与化疗相关的长期血管毒性包括雷诺现象、急性心肌梗死和脑血管事件。博来霉素被认为是雷诺现象发病机制中最重要的药物，而顺铂是最可能与心肌梗死有关的药物。周围神经病变是基于顺铂化疗观察到的最常见的神经毒性形式。神经损伤发生的危险因素包括顺铂的高累积剂量、长春花碱的使用以及同时出现的雷诺现象。顺铂还因会导致显著的肾毒性而闻名。接受联合化疗并随访2至5年的患者中，约25%会出现无精子症。医生了解化疗相关并发症对于最大化疗效、最小化毒性以及治疗后维持生活质量至关重要。对于想要孩子的患者应考虑精子冷冻保存。治疗期间密切监测有助于早期诊断并发症，治疗结束后对患者进行密切随访对于监测复发以及长期并发症如骨髓增生异常综合征和白血病的发生是必要的。尽管有这些并发症，但鉴于这一年轻患者群体有治愈的可能性，益处远远超过风险。
