Freytag Svend O, Movsas Benjamin, Aref Ibrahim, Stricker Hans, Peabody James, Pegg Jan, Zhang Yingshu, Barton Kenneth N, Brown Stephen L, Lu Mei, Savera Adnan, Kim Jae Ho
Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan 48202, USA.
Mol Ther. 2007 May;15(5):1016-23. doi: 10.1038/mt.sj.6300120. Epub 2007 Mar 20.
Replication-competent adenovirus-mediated suicide gene therapy is an investigational cancer treatment in which an oncolytic adenovirus armed with chemo-radiosensitizing genes is used to destroy tumor cells. Previously, we evaluated the toxicity and efficacy of this approach in two clinical trials of prostate cancer using a first-generation adenovirus. Here, we report the toxicity and preliminary efficacy of this approach in combination with intensity-modulated radiotherapy (IMRT) in patients with newly diagnosed prostate cancer using an improved, second-generation adenovirus. The investigational therapy was associated with low toxicity, and there were no dose-limiting toxicities or treatment-related serious adverse events. Relative to a previous trial using a first-generation adenovirus, there was no increase in hematologic, hepatic, gastrointestinal (GI), or genitourinary (GU) toxicities. Post-treatment prostate biopsies yielded provocative preliminary results. When the results of two similar trials were combined, 22% of evaluable patients were positive for adenocarcinoma at their last biopsy, which is better than expected (>or=40%) for this cohort of patients (P=0.038). When the results were categorized by prognostic risk, most of the treatment effect was observed in the intermediate-risk group, with 0 of 12 patients (0%) being positive for cancer at their last biopsy (P<0.01). These results further demonstrate the safety of this investigational approach and raise the possibility that it may have the potential to improve the outcome of conformal radiotherapy in select patient groups.
具有复制能力的腺病毒介导的自杀基因疗法是一种正在研究的癌症治疗方法，其中携带化学放射增敏基因的溶瘤腺病毒用于破坏肿瘤细胞。此前，我们在两项前列腺癌临床试验中使用第一代腺病毒评估了这种方法的毒性和疗效。在此，我们报告了使用改良的第二代腺病毒，这种方法联合调强放疗（IMRT）在新诊断前列腺癌患者中的毒性和初步疗效。该研究性疗法毒性较低，没有剂量限制性毒性或与治疗相关的严重不良事件。相对于之前使用第一代腺病毒的试验，血液学、肝脏、胃肠道（GI）或泌尿生殖系统（GU）毒性没有增加。治疗后的前列腺活检产生了令人鼓舞的初步结果。当两项类似试验的结果合并时，22%的可评估患者在最后一次活检时腺癌呈阳性，这优于该组患者的预期（≥40%）（P=0.038）。当按预后风险对结果进行分类时，大部分治疗效果在中危组中观察到，12名患者中有0名（0%）在最后一次活检时癌症呈阳性（P<0.01）。这些结果进一步证明了这种研究方法的安全性，并增加了它可能有潜力改善特定患者群体适形放疗结果的可能性。
