Clinical response in metastatic castration‐resistant prostate cancer (mCRPC) cases treated with supra‐physiological doses of testosterone: Bipolar androgen therapy

Hoshi, Senji; Bilim, Vladimir; Hoshi, Kiyotsugu; Nakagawa, Takuya; Sato, Sadanobu; Sakagami, Rie; Konno, Masashi; Kudo, Takashi; Numahata, Kenji; Sasagawa, Isoji

doi:10.1002/ccr3.5433

Cited by 3 publications

(4 citation statements)

References 13 publications

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“…This was due to the heterogeneity of the enrolled patients and the unequal sample size. In these ten studies, PSA50 ranged from 14% in the study by Laura A. Sena et al (17)to 100% in the report by Senji Hoshi et al (18). Shown in Figure 2, a total of 353 patients were included, and the overall PSA50 response rate was 27% (95%CI [0.22,0.31], I 2 = 17.98%).…”

Section: Results Of Psa50mentioning

confidence: 99%

“…However, some studies included in this study (such as the case reports of Senji et al (18) and Liu et al (24) may have an impact on the results of this study due to the small number of cases. The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 96%

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Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review

et al. 2023

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Bipolar androgen therapy (BAT) is a new endocrinologic treatment for castration-resistant prostate cancer (CRPC) that can restore some patients’ sensitivity to drugs such as abiraterone (Abi) and enzalutamide (Enz). We performed a meta-analysis using STATA16. Sensitivity analyses were performed by examining the effects of individual studies using different effect models and detecting any publication bias using the Harbord test. In a total of 108 unique records, ten studies were included in the final meta-analysis. Participants who underwent BAT achieved a PSA50 response rate of 27% (95%CI [0.22,0.31], I2=17.98%), ORR of 34% (95%CI [0.24,0.43], I2=0), and incidence of AEs (grade≥3) of 14% (95%CI [0.09,0.19], I2=0). Patients who completed BAT proceeded to AR-targeted therapy (Abi or Enz) and achieved a PSA50 response rate of 57% (95% CI [0.36,0.78], I2=0). Patients with prior Enz resistance had a stronger impact on the PSA50 of AR-target therapy rechallenge. The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz. BAT can trigger the resensitization of patients with CRPC to subsequent endocrine therapy and improve the overall survival of patients and their quality of life.

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Section: Results Of Psa50mentioning

confidence: 99%

Section: Discussionmentioning

confidence: 95%

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Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review

et al. 2023

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“…Bipolar androgen therapy (BAT) was reported in the treatment of castrate-resistant prostate cancer (CRPC) [69][70][71][72][73][74][75][76]. Treating CRPC patients with testosterone cypionate and etoposide on top of androgen deprivation therapy resulted in high rates of PSA and radiographic responses, although all men showed eventual PSA progression [69].…”

Section: Supraphysiologic Testosterone Therapy In the Treatment Of Pr...mentioning

confidence: 99%

Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer

Nasser

2022

Cancers

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Treatment of metastatic prostate cancer was historically performed via bilateral orchiectomy to achieve castration. An alternative to surgical castration is the administration of subcutaneous recombinant luteinizing hormone-releasing hormone (LHRH). LHRH causes the pituitary gland to produce luteinizing hormone (LH), which results in synthesis and secretion of testosterone from the testicles. When LHRH levels are continuously high, the pituitary gland stops producing LH, which results in reduced testosterone production by the testicles. Long-acting formulations of LHRH were developed, and its use replaced surgical orchiectomy in the vast majority of patients. Combining LHRH and radiation therapy was shown to increase survival of prostate cancer patients with locally advanced disease. Here, we present a hypothesis, and preliminary evidence based on previous randomized controlled trials, that androgen surge during radiation, rather than its suppression, could be responsible for the enhanced prostate cancer cell kill during radiation. Starting LHRH agonist on the first day of radiation therapy, as in the EORTC 22863 study, should be the standard of care when treating locally advanced prostate cancer. We are developing formulations of short-acting LHRH agonists that induce androgen flare, without subsequent androgen deprivation, which could open the door for an era in which prostate cancer could be cured while patients maintain potency.

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Bipolar androgen therapy for treatment of metastatic castration‐resistant prostate cancer: A case series

Tran,

Royz,

Yamamoto

et al. 2024

The Prostate

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IntroductionAdvanced prostate cancer treatment has improved with androgen receptor signaling inhibitors (ARPI), yet many patients develop metastatic castration‐resistant prostate cancer (mCRPC), characterized by sustained androgen receptor (AR) signaling. Bipolar androgen therapy (BAT) introduces supraphysiologic testosterone levels to inhibit tumor growth, offering novel treatment for mCRPC by exploiting AR‐dependent mechanisms.Case PresentationsCase 1: A 53‐year‐old man with mCRPC, post multiple systemic therapies, initiated BAT and pembrolizumab, achieving PSA reduction and improved quality of life before progression. The patient exhibited AR amplification, which may have contributed to favorable response to BAT.Case 2: A 73‐year‐old man with recurrent prostate cancer, stable on ADT and abiraterone, experienced PSA decline with BAT to an undetectable level, maintaining stability post‐therapy discontinuation.Case 3: A 73‐year‐old man with metastatic prostate cancer, initially resistant to enzalutamide, achieved clinical benefit and disease control with BAT, although he did not meet PSA response criteria, patient had remarkable response upon enzalutamide rechallenge.Case 4: A 90‐year‐old man with localized prostate cancer, refractory to multiple treatments, experienced symptom relief and PSA reduction with BAT before progression.ConclusionBAT represents a promising treatment strategy for mCRPC. This case series underscores BAT's potential to induce significant clinical and biochemical responses, resensitize tumors to ARPIs, and improve patients' quality of life. Despite eventual progression in some cases, BAT offers a period of disease control. Further research is needed to optimize patient selection and understand the molecular determinants of BAT responsiveness.

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Clinical response in metastatic castration‐resistant prostate cancer (mCRPC) cases treated with supra‐physiological doses of testosterone: Bipolar androgen therapy

Cited by 3 publications

References 13 publications

Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review

Efficacy and safety of bipolar androgen therapy in castration-resistant prostate cancer following abiraterone or enzalutamide resistance: A systematic review

Androgen Flare after LHRH Initiation Is the Side Effect That Makes Most of the Beneficial Effect When It Coincides with Radiation Therapy for Prostate Cancer

Bipolar androgen therapy for treatment of metastatic castration‐resistant prostate cancer: A case series

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