Banna Giuseppe Luigi, Simonelli Matteo, Santoro Armando
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni, 56, 20089 Rozzano, Milano, Italy.
Curr Stem Cell Res Ther. 2007 Jan;2(1):65-82. doi: 10.2174/157488807779316964.
High-dose chemotherapy (HDCT) plus autologous hematopoietic stem-cell transplantation (HSCT) has been explored in several solid tumors in the attempt to prevent and/or overcome tumor-cell chemo-resistance, based on in vitro evidence of a "dose-response" effect. Preliminary encouraging results from non-randomized trials, led to an increased use of this strategy in the 1990s. Since the end of the nineties, the fraudulent nature of initial reports in breast cancer, the failure of positive prospective randomized trials, HDCT-related toxicities, determined a dramatic decline of interest in this approach. Loss of accrual in ongoing randomized studies was the first consequence, causing the current unavailability of optimal information. From the review of available published data, the use of HDCT with autologous HSCT may improve tumor response rates and/or possibly progression-free survival, especially in some selected patient subgroups. However, this strategy did not demonstrate in almost all cases to produce significantly higher cure rates than standard-dose chemotherapy. Well-designed randomized studies and future strategies integrating HDCT with concomitant and/or subsequent anti-tumor therapies targeted against the residual disease might be suggested in clinically and biologically selected patients.
基于“剂量反应”效应的体外证据,高剂量化疗(HDCT)联合自体造血干细胞移植(HSCT)已在多种实体瘤中进行了探索,旨在预防和/或克服肿瘤细胞的化疗耐药性。非随机试验的初步令人鼓舞的结果,使得该策略在20世纪90年代的使用有所增加。自90年代末以来,乳腺癌初始报告的欺诈性质、阳性前瞻性随机试验的失败以及HDCT相关的毒性,导致人们对这种方法的兴趣急剧下降。正在进行的随机研究中入组人数的减少是首要后果,导致目前无法获得最佳信息。从对已发表的可用数据的回顾来看,使用HDCT联合自体HSCT可能会提高肿瘤缓解率和/或可能改善无进展生存期,特别是在一些选定的患者亚组中。然而,在几乎所有情况下,该策略并未显示出比标准剂量化疗产生显著更高的治愈率。对于临床和生物学上选定的患者,可能建议进行精心设计的随机研究以及未来将HDCT与针对残留疾病的同步和/或后续抗肿瘤治疗相结合的策略。