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.
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