Bipolar androgen therapy (BAT) relies on oscillating levels of serum testosterone as a way to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Aggressive-variant prostate cancers typically require combination chemotherapy and are frequently associated with loss-of-function mutations in tumor suppressor genes. Here we report clinical outcomes after BAT among patients with mCRPC harboring pathogenic alterations in at least two of three genes: TP53, PTEN, and RB1. In this setting, BAT induced a meaningful PSA50 response rate, progression-free survival and overall survival, particularly in patients without prior chemotherapy. Patient summary: Bipolar androgen therapy, in which drugs are used to raise testosterone levels and then allow them to decrease again in a cycle, may be a safe and effective treatment for prostate cancer that is resistant to testosterone suppression and has mutations in tumor suppressor genes. A randomized study comparing this approach to chemotherapy is needed to confirm the findings.
Bibliographical noteFunding Information:
Financial disclosures: Mark C. Markowski certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Michael T. Schweizer is a paid consultant for AstraZeneca, PharmaIn, and Resverlogix, and has received institutional research funding from Zenith Epigenetics, Bristol-Myers Squibb, Merck, Immunomedics, Janssen, AstraZeneca, Pfizer, Madison Vaccines, Hoffman-La Roche, Tmunity, SignalOne Bio, and Ambrx. Emmanuel S. Antonarakis is a paid consultant/advisor for Amgen, AstraZeneca, Bayer, Blue Earth, Bristol-Myers Squibb, Celgene, Clovis, Constellation, Curium, Eli Lilly, ESSA, Exact Sciences, Foundation Medicine, GlaxoSmithKline, Invitae, Janssen, Johnson & Johnson, Merck, Sanofi, and Tempus, and is co-inventor of a biomarker technology licensed to Qiagen. Samuel R. Denmeade has received research funding from Astellas. Mark C. Markowski is a paid consultant for Clovis and Exelixis. Hao Wang and Angelo M. De Marzo have nothing to disclose.
Funding/Support and role of the sponsor: This project was supported by the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins National Institutes of Health grant P30 CA006973, R01 CA184012, a PCF Challenge Award, and an Allegheny Health Network Award. The sponsors played a role in the design and conduct of the study. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
© 2022 The Author(s)
- Aggressive variant
- AR indifferent
PubMed: MeSH publication types
- Journal Article