Five-year follow-up of trial of replication-competent adenovirus-mediated suicide gene therapy for treatment of prostate cancer
Five-year follow-up of trial of replication-competent adenovirus-mediated suicide gene therapy for treatment of prostate cancer
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DOI：
10.1038/sj.mt.6300068
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发表时间：
2007-03-01
影响因子：
12.4
通讯作者：
Kim, Jae Ho
中科院分区：
文献类型：
--
作者：
Freytag, Svend O.;Stricker, Hans;Kim, Jae Ho
复制型腺病毒介导的自杀基因治疗是一种研究性的癌症治疗方法，它结合了人腺病毒的溶瘤作用和化疗-放射增敏基因的细胞毒性作用。以前，我们报道了这种疗法在确定性放疗后局部复发的前列腺癌患者中的短期效果。前列腺特异性抗原（PSA）随访中位数为5年，我们在此报告基因治疗对前列腺特异性抗原倍增时间（PSADT）的影响，PSADT是一个具有显著预后能力的替代终点。当考虑所有可评估的受试者时，基因治疗后PSADT从平均17个月增加到31个月（中位数16个月至22个月）（P = 0.014）。假设挽救性雄激素抑制治疗（AST）在PSA <15 ng/mL时开始，基因治疗将使挽救性治疗的预计开始时间平均延迟2年。结果表明，复制型腺病毒介导的自杀基因治疗可能为患者提供潜在的长期益处，如PSADT延长所示，并延迟挽救治疗。鉴于AST相关的高发病率，我们认为这种方法可以为选择在确定性治疗后发生PSA复发的患者提供有吸引力的治疗选择。
Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment that combines the oncolytic actions of human adenoviruses with the cytotoxic effects of chemo-radiosensitizing genes. Previously, we reported the short-term effects of this therapy in men with local recurrence of prostate cancer after definitive radiotherapy. With a median prostate-specific antigen (PSA) follow-up of 5 years, we report here the effect of the gene therapy on prostate-specific antigen doubling time (PSADT), a surrogate end point with significant prognostic power. When considering all evaluable subjects, the PSADT increased following the gene therapy from a mean of 17 to 31 months ( median 16 to 22 months) ( P = 0.014). Assuming that salvage androgen suppression therapy androgen suppression therapy (AST) was uniformly initiated at a PSA of 15 ng/mL, the gene therapy would have delayed the projected onset of salvage therapy by an average of 2 years. The results indicate that replication-competent adenovirus-mediated suicide gene therapy may provide a potential long-term benefit to patients, as shown by a lengthening of the PSADT, and delay in when salvage therapy is indicated. Given the high morbidity associated with AST, we believe this approach could provide an attractive treatment option for selection of patients experiencing PSA relapse following definitive therapy.