A Mechanistic Study to Explain the Survival Benefit of Chemo-Hormonal Therapy in Metastatic Castration-Sensitive Prostate Cancer
Abstract
This project is focused on developing better therapies for patients with metastatic disease. Specifically, in the ECOG led trial, E3805: CHAARTED, it was shown that docetaxel added at the time of starting testosterone suppression resulted in an increase in average survival from 44 months to 57 months. The underlying mechanism for this major finding is unknown. This project is designed to define the changes that occur in the cells that make them more sensitive to docetaxel at time of starting testosterone suppression rather than adding it on when a patient s cancer is growing again in the face of ongoing testosterone suppression. The potential clinical applications of this work is that it will provide information on who best to treat with the more intense therapy of testosterone suppression with early chemotherapy rather than testosterone suppression alone. This will allow physicians to match the best treatment plan for an individual patient. It is projected we will define the cellular changes underlying the changes in the 3 years of the proposed project. The immediate possible patient-related outcome is guiding which patients benefit from early chemotherapy with its associated side effects versus those who can be treated with testosterone suppression alone and have the same degree of cancer control. Likely longer-term contributions of this study to advancing the field of prostate cancer research include identifying the cellular mechanisms underlying the positive findings seen in the E3805 trial. This will then provide guidance to scientists regarding the best combination of drugs to use, targets to guide development of new drugs against as well as guide the best time and/or tumor profile to deploy chemotherapy. For example, if we can identify the factors underlying the marked activity of docetaxel in hormone-sensitive prostate cancer, we can attempt to recapitulate this in castration-resistant prostate cancer and make chemotherapy more active in castration-resistant prostate cancer as well or develop a strategy to make cells chemosensitive in hormone-sensitive prostate cancer without having to also have the long-term side effects of testosterone suppression.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610639
Entities
People
- Christopher Sweeney
Organizations
- Dana–Farber Cancer Institute
- United States Army