Drug development for noncastrate prostate cancer in a changed therapeutic landscape Journal Article
| Authors: | Teo, M. Y.; O'Shaughnessy, M. J.; McBride, S. M.; Vargas, H. A.; Scher, H. I. |
| Article Title: | Drug development for noncastrate prostate cancer in a changed therapeutic landscape |
| Abstract: | The unprecedented progress in the treatment of metastatic castration-resistant prostate cancer is only beginning to be realized in patients with noncastrate disease. This slow progress in part reflects the use of trial objectives focused on time-To-event end points, such as time to metastasis and overall survival, which require long follow-up durations and large sample sizes, and has been further delayed by the use of approved therapies that are effective at the time of progression. Our central hypotheses are that progress can be accelerated, and that outcomes can be improved by shifting trial objectives to response measures occurring early that solely reflect the effects of the treatment. To test these hypotheses, a continuously enrolling multi-Arm, multi-stage randomized trial design, analogous to that used in the STAMPEDE trial, has been developed. Eligibility is focused on patients with incurable disease or those with a high risk of death with any form of monotherapy alone. The primary objective is to eliminate all disease using a multimodality treatment strategy. End points include pathological complete response and an undetectable level of serum prostate-specific antigen, with recovery of serum testosterone levels. Both are binary, objective, and provide an early, quantitative indication of efficacy. © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserve. |
| Keywords: | cancer chemotherapy; cancer survival; survival rate; overall survival; prednisone; review; cancer localization; advanced cancer; multimodality cancer therapy; cancer radiotherapy; cancer staging; nuclear magnetic resonance imaging; positron emission tomography; treatment indication; prostate specific antigen; metastasis; progression free survival; cancer mortality; docetaxel; prostate cancer; gleason score; goserelin; leuprorelin; survival time; drug research; minimal residual disease; prostatectomy; clinical research; cyproterone; high risk population; bicalutamide; dutasteride; flutamide; ketoconazole; testosterone blood level; testosterone; biochemical recurrence; castration resistant prostate cancer; recurrence free survival; abiraterone; enzalutamide; metastasis free survival; human; priority journal; x-ray computed tomography |
| Journal Title: | Nature Reviews Clinical Oncology |
| Volume: | 15 |
| Issue: | 3 |
| ISSN: | 1759-4774 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2018-03-01 |
| Start Page: | 168 |
| End Page: | 182 |
| Language: | English |
| DOI: | 10.1038/nrclinonc.2017.160 |
| PROVIDER: | scopus |
| PUBMED: | 29039422 |
| DOI/URL: | |
| Notes: | Review -- Export Date: 2 April 2018 -- Source: Scopus |
