Evidence map›Paper›PMID 29248236›Full record

Trial reportThe Lancet. Oncology2018

Bipolar androgen therapy in men with metastatic castration-resistant prostate cancer after progression on enzalutamide: an open-label, phase 2, multicohort study.

Benjamin A Teply, Hao Wang, Brandon Luber, Rana Sullivan, Irina Rifkind, Ashley Bruns, Avery Spitz, Morgan DeCarli, Victoria Sinibaldi, Caroline F Pratz and 10 more

2 registry-linked trialsOpen access · greenAbstract readClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 110 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
110citing papers in PubMed, 4 pooled it
15.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02090114 phase2completednot on this map

A Phase II Study to Determine Sequential Response to Bipolar Androgen Therapy (BAT) Followed by Enzalutamide or Abiraterone Post-BAT in Men With Prostate Cancer Progressing on Combined Androgen Ablative Therapies

TypeinterventionalSponsorSidney Kimmel Comprehensive Cancer Center at Johns HopkinsRan2014 to 2021Enrolled112ConditionsProstate CancerArmsTestosterone cypionate, Testosterone Enanthate, Abiraterone acetate, Enzalutamide
NCT03522064 phase2recruitingnot on this map

High Dose Testosterone + Carboplatin in Men With Advanced Prostate Cancer

TypeinterventionalSponsorSt Vincent's Hospital, SydneyRan2018 to 2027Enrolled30ConditionsCastration-resistant Prostate Cancer, Homologous Recombination DeficiencyArmsTestosterone Enanthate 100 MG/ML Injectable Solution, Testosterone Enanthate 100 MG/ML Injectable Solution / Carboplatin AUC 5
3 · Its place in the literature

Who cites it

110 citing papers in PubMed, 4 syntheses or guidelines pooled it, 194 citations in OpenAlex.

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  13. Lack of synergy between AR-targeted therapies and PARP inhibitors in homologous recombination-proficient prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026
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50 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 3 institutions in 1 country.

Benjamin A TeplyDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Oncology and Hematology, University of Nebraska Medical Center, Omaha, NE, USA.
Hao WangDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brandon LuberDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Rana SullivanDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Irina RifkindDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ashley BrunsDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Avery SpitzDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Morgan DeCarliDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Victoria SinibaldiDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Caroline F PratzDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Changxue LuDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
John L SilbersteinDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jun LuoDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Michael T SchweizerDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, Division of Oncology, University of Washington, Seattle, WA, USA.
Charles G DrakeDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Division of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA.
Michael A CarducciDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Channing J PallerDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Emmanuel S AntonarakisDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Mario A EisenbergerDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Samuel R DenmeadeDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: denmesa@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · USUniversity of Washington · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI WILLIAM George NELSON · 1985 to 2026
$208.6M
Bipolar Androgen Therapy for Progressive Castrate Resistant Prostate CancerR01CA184012 · NCI · JOHNS HOPKINS UNIVERSITY · PI DENMEADE, SAMUEL R · 2014 to 2018
$1.3M
NCI NIH HHS P30 CA006973NCI NIH HHS R01 CA184012
6 · The paper itself

Abstract

backgroundProstate cancer that progresses after enzalutamide treatment is poorly responsive to further antiandrogen therapy, and paradoxically, rapid cycling between high and low serum testosterone concentrations (bipolar androgen therapy [BAT]) in this setting might induce tumour responses. We aimed to evaluate BAT in patients with metastatic castration-resistant prostate cancer that progressed after enzalutamide.

methodsWe did this single-centre, open-label, phase 2, multicohort study in the USA. We included patients aged 18 years or older who had histologically confirmed and radiographically documented metastatic castration-resistant prostate cancer, with no more than two previous second-line hormonal therapies, and a castrate concentration of testosterone. Patients were asymptomatic, with Eastern Cooperative Oncology Group performance status of 0-2, and did not have high-risk lesions for tumour flare (eg, >5 sites of visceral disease or bone lesions with impending fracture). For the cohort reported here, we required patients to have had progression on enzalutamide with a continued prostate-specific antigen (PSA) rise after enzalutamide treatment discontinuation. Patients received BAT, which consisted of intramuscular testosterone cipionate 400 mg every 28 days until progression and continued luteinising hormone-releasing hormone agonist therapy. Upon progression after BAT, men were rechallenged with oral enzalutamide 160 mg daily. The co-primary endpoints were investigator-assessed 50% decline in PSA concentration from baseline (PSA

findingsBetween Aug 28, 2014, and May 18, 2016, we accrued 30 eligible patients and treated them with BAT. Nine (30%; 95% CI 15-49; p<0·0001) of 30 patients achieved a PSA

interpretationBAT is a safe therapy that resulted in responses in asymptomatic men with metastatic castration-resistant prostate cancer and also resensitisation to enzalutamide in most patients undergoing rechallenge. Further studies with BAT are needed to define the potential clinical role for BAT in the management of metastatic castration-resistant prostate cancer and the optimal strategy for sequencing between androgen and antiandrogen therapies in metastatic castration-resistant prostate cancer to maximise therapeutic benefit to patients.

fundingNational Institutes of Health and National Cancer Institute.

Indexed as

AgedAged, 80 and overAndrogensAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBaltimoreBenzamidesDisease ProgressionGonadotropin-Releasing HormoneHumansKallikreinsMaleMiddle AgedNeoplasm MetastasisNitrilesPhenylthiohydantoinAndrogensAntineoplastic Agents, HormonalBenzamidesenzalutamideGonadotropin-Releasing HormoneKallikreinsKLK3 protein, humanNitrilesPhenylthiohydantoinProstate-Specific AntigenTestosteronetestosterone 17 beta-cypionate

Identifiers

PMID29248236
PMCPMC5875180
OpenAlexW2772636479

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.