Dataset Information

Bipolar androgen therapy (BAT): A patient's guide.

ABSTRACT: Bipolar androgen therapy (BAT) is a new treatment concept for men whose prostate cancer has become resistant to standard hormone-blocking therapy. Over the past decade, we have performed a series of clinical studies testing BAT in asymptomatic men with castration-resistant prostate cancer. The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic castrate-resistant prostate cancer; (b) does not produce symptomatic disease progression; (c) produces sustained prostate-specific antigen and objective responses in 30%-40% of patients; and (d) can resensitize and prolong response to subsequent antiandrogen therapy. The concept of BAT has generated significant interest from men with prostate cancer, their families, and their physicians. Here we provide a "Patient's Guide" that answers questions about BAT in a form that is accessible to patients, their families, and physicians. Our goal is to provide information to help patients make the most informed decisions they can regarding their prostate cancer treatment.

SUBMITTER: Denmeade S

PROVIDER: S-EPMC9313844 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bipolar androgen therapy (BAT): A patient's guide.

Denmeade Samuel S Antonarakis Emmanuel S ES Antonarakis Emmanuel S ES Markowski Mark C MC

The Prostate 20220331 7

Bipolar androgen therapy (BAT) is a new treatment concept for men whose prostate cancer has become resistant to standard hormone-blocking therapy. Over the past decade, we have performed a series of clinical studies testing BAT in asymptomatic men with castration-resistant prostate cancer. The key findings from these clinical studies are that BAT (a) can be safely administered to asymptomatic patients with metastatic castrate-resistant prostate cancer; (b) does not produce symptomatic disease pr ...[more]

PMID: 35357024

Similar Datasets

Project description:Inhibition of androgen receptor (AR) signaling has been the mainstay of treatment of advanced prostate cancer (PCa) for the past 80 years. Combination and sequential AR-inhibiting therapies are highly effective palliative therapy, but they are not curative. All patients eventually develop resistance to primary castrating therapy [ie, castration-resistant PCa (CRPC)]. At this point, they are treated with subsequent lines of secondary AR inhibitory therapies. However, resistance to these agents also develops and patients progress to a state we have termed complete androgen inhibition-resistant PCa. This phase of the disease is associated with poor prognosis. At this point, treatment shifts to non-hormonal cytotoxic therapies (eg, chemotherapy and radiopharmaceuticals). However, the majority of PCas remain addicted to signaling through AR throughout the course of the disease. Resistant PCa cells adaptively upregulate AR activity, despite castration and AR inhibitors, via mechanisms such as AR overexpression, gene amplification, mutation, and expression of ligand-independent variants to permit sustained liganded and non-liganded AR signaling. Studies dating back nearly 30 years indicate that high expression of AR induced by prolonged castration becomes a vulnerability of CRPC cells in vitro and in mouse xenografts to supraphysiologic androgen (SPA), which induces cell death and growth arrest in this context. Based on these studies, we developed a counterintuitive treatment called bipolar androgen therapy (BAT) for patients with CRPC, in which SPA is administered intermittently to result in cycling of serum testosterone from the polar extremes of supraphysiologic to near-castrate levels. This rapid cycling is intended to disrupt the adaptive of AR regulation associated with chronic exposure to high or low levels of testosterone, while simultaneously targeting the spectrum of AR expression present in heterogeneous CRPC tumors. We have now tested BAT in >250 patients with CRPC. Here we present a review of these clinical studies, which have demonstrated collectively that BAT can be safely given to men with CRPC, improves quality of life, and produces therapeutic responses in ~30% of patients. As expected, resistance to BAT is associated with adaptive downregulation of AR expression. Intriguingly, this downregulation is associated with restoration of sensitivity to subsequent AR inhibitor therapies.

Project description:BackgroundRelugolix is the newest form of androgen deprivation therapy (ADT) approved for prostate cancer. However, as an oral drug, several real-world concerns exist, particularly medication compliance, safety with other androgen receptor-targeted agents, and financial burden to patients.MethodsA single institution retrospective chart review was conducted evaluating all patients who were prescribed relugolix for any prostate cancer indication from January 1, 2021 to January 31, 2022. Demographic data, cardiac risk factors, concomitant therapy usage, and PSA/testosterone levels, were abstracted from the chart review. Adverse effects were obtained by examining progress notes. Compliance was assessed by clinic notes as well as prescription fills by specialty pharmacy records. The reasons patients did not fill or discontinued the medication were noted.ResultsHundred and one patients were prescribed relugolix, and 91 patients consented to research. Seventy-one (78%) patients filled the prescription to relugolix, with a median follow-up of 5 months. Prescription fill data were available for 45 (63%) patients, with 94% of days covered. The most commonly reported reason not to fill was cost at 50%. Sixty-six (93%) patients reported never missing a dose. PSA levels were available in 71 (100%) patients with 69 (97%) showing stable or improved PSA. Testosterone levels were available in 61 (86%) of patients, which showed 61 (100%) stable or successful castration. Twenty-four (34%) patients used relugolix in combination. No new major safety signals were seen in combination therapy. Nineteen (27%) patients had switched to another form of ADT. Fifteen of these (79%) felt similar or better on relugolix therapy.ConclusionsCompliance with relugolix seemed acceptable. No major new safety signals were seen, even in combination. Among patients who switched therapy, most tolerated relugolix similarly or better than the previous form of ADT. The cost was a major reason for patients not initiating and for discontinuing therapy.

Dataset Information

Bipolar androgen therapy (BAT): A patient's guide.

Publications

Bipolar androgen therapy (BAT): A patient's guide.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets