Bastos Diogo A, Feldman Darren R
aGenitourinary Oncology, Oncology Center, Hospital Sirio-Libanes, Sao Paulo, Brazil bGenitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center cDepartment of Medicine, Weill Medical College of Cornell University, New York, New York, USA.
Curr Opin Oncol. 2014 May;26(3):284-93. doi: 10.1097/CCO.0000000000000070.
To discuss the current role and future perspectives of high-dose chemotherapy (HDCT) in the management of advanced germ cell tumors (GCTs).
Multiple studies have demonstrated the safety and efficacy of HDCT, consisting of carboplatin and etoposide followed by stem cell reinfusion, for the salvage treatment of GCTs. However, three randomized trials showed no benefit for HDCT over conventional dose chemotherapy in the first-line setting. Similarly, adding a third drug to etoposide with carboplatin does not seem to substantially improve treatment efficacy and may increase toxicity and mortality. Recent retrospective data from single centers and a large international collaboration demonstrated better outcomes with use of HDCT in the initial (rather than later) salvage setting as well as with sequential rather than single cycle regimens. However, randomized data are lacking. Prognostic factors for outcome to salvage HDCT were recently established and enhanced supportive measures such as growth factors and antibiotic prophylaxis have resulted in a dramatic decrease in morbidity and mortality.
HDCT plays an integral role in the salvage treatment of patients with advanced GCTs. However, optimal timing (initial vs. later salvage), dosing, number of high-dose cycles, and patient selection remain to be defined.
探讨大剂量化疗(HDCT)在晚期生殖细胞肿瘤(GCT)治疗中的当前作用及未来前景。
多项研究已证实,由卡铂和依托泊苷组成并随后进行干细胞回输的HDCT用于GCT挽救治疗的安全性和有效性。然而,三项随机试验表明,在一线治疗中,HDCT并不比传统剂量化疗更具优势。同样,在依托泊苷与卡铂的基础上加用第三种药物似乎并不能显著提高治疗效果,反而可能增加毒性和死亡率。来自单中心的近期回顾性数据以及一项大型国际合作研究表明,在初始(而非后期)挽救治疗中使用HDCT以及采用序贯而非单周期方案可取得更好的疗效。然而,缺乏随机数据。近期已确定了挽救性HDCT治疗结果的预后因素,并且诸如生长因子和抗生素预防等强化支持措施已使发病率和死亡率显著降低。
HDCT在晚期GCT患者的挽救治疗中发挥着不可或缺的作用。然而,最佳时机(初始挽救与后期挽救)、剂量、大剂量周期数以及患者选择仍有待确定。