BI-WEEKLY TAXOL & RT IN ANDROGEN ABLATED ADVANCED PROSTATE CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。这是一项研究雄激素消融前列腺癌的明确放疗治疗的方案，并添加赫赛汀。先前的研究表明，雄激素阻断在许多情况下可显著减少肿瘤体积，在减少局部进展和无病生存的措施上，与放疗联合使用明显优于单独放疗。然而，结果并不理想，因为在许多患者中很难检测到进展，并且可能仅通过PSA升高来指示。还需要其他方法。赫赛汀是一种针对Her-2/神经受体的人源化单克隆抗体，在乳腺癌治疗中显示出前景。雄激素消融可诱导Her2/neu过表达（一个不希望的结果），并引起放射增敏，从而更好地局部控制和无病生存（一个理想的结果）。赫赛汀通过与受体结合，可能干扰Her-2/neu的表达，因此是有益的。这项剂量递增的i期研究为那些被认为过于晚期而不能进行手术切除且通常接受雄激素消融和放射治疗的患者每周两次增加低剂量（在队列中逐步增加）紫杉醇。这些剂量的紫杉醇应该不会增加毒性，除非通过放射致敏。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a protocol to study the treatment of prostate cancer with definitive radiotherapy applied to androgen-ablated prostate cancer, with the addition of Herceptin. Prior studies have revealed that androgen blockade, which significantly reduces tumor volume in many cases, in combination with radiation is significantly better than radiation alone in measures on decrease in local progression and disease-free survival. Results are less than optimal, however, since progression is hard to detect in many patients and may only be indicated by a rise in PSA. Additional methodologies are required. Herceptin is a humanized monoclonal antibody that targets the Her-2/neuroreceptor and has shown promise in breast cancer. Androgen ablation could induce Her2/neu overexpression (an undesirable outcome) and cause radiosensitization resulting in better local control and disease-free survival (a desirable outcome). Herceptin, by binding to the receptor, may interfere with the expression of Her-2/neu and therefore be of benefit. This dose-escalation phase-I study adds low doses (increasing stepwise in cohorts) of Taxol twice a week to patients deemed too advanced for surgical resection and who are usually treated with androgen ablation and radiation. Taxol at these doses should add little toxicity, except through radiosensitization.