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| Fig. 3.
Evaluation of clinical response.
(A) Waterfall plot showing maximum PSA change relative to baseline in 14 patients completing at least three cycles of BAT plus etoposide. The number at the end of each bar indicates the number of treatment cycles received. The number in parentheses indicates the percent PSA change in a case where the bar was truncated. (B) Patterns of PSA response observed in patients on study. (C) PSA response in an individual patient (patient 9) receiving a total of 16 cycles of BAT. (D) Computed tomography (CT) scans obtained before treatment and after three cycles of therapy in two patients on study, demonstrating complete response (CR) (patient 16, upper panels) and partial response (PR) (patient 15, lower panels) in abdominal lymph nodes. Red circles outline disease burden. |
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| Fig. 2.
Clinical trial of BAT plus etoposide.
(A) Schematic of study design.
(B) Baseline characteristics of patients on study. (C) Mean serum testosterone levels at indicated time points for patients on study. |
Man 'cured' of prostate cancer after doctors shock tumour to death with testosterone
A man with advanced prostate cancer is believed to be cured after doctors 'shocked' his tumour to death with huge amounts of testosterone.
The result has been described as 'unexpected' and 'exciting' because most prostate cancer therapies work by depriving tumours of testosterone, because cancer uses it as a fuel. Other seriously ill men taking part in the same trial showed responses that astounded scientists, with tumours shrinking and the progress of their disease halted.
Levels of Prostate Specific Antigen (PSA), a blood marker used to monitor prostate cancer, also fell in the majority of the 47 participants.
One individual whose PSA levels dropped to zero after three months and shows no remaining trace of the disease after 22 cycles of treatment appears to be cured, said the researchers.
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| Sam Denmeade, M.D. |
Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: Results from a pilot clinical study | Science Translational Medicine
Abstract: Targeting androgen receptor (AR) axis signaling by disrupting androgen-AR interactions remains the primary treatment for metastatic prostate cancer. Unfortunately, all men develop resistance to primary castrating therapy and secondary androgen deprivation therapies (ADTs). Resistance develops in part because castration-resistant prostate cancer (CRPC) cells adaptively up-regulate AR levels through overexpression, amplification, and expression of ligand-independent variants in response to chronic exposure to a low-testosterone environment. However, preclinical models suggest that AR overexpression represents a therapeutic liability that can be exploited via exposure to supraphysiologic testosterone to promote CRPC cell death. Preclinical data supported a pilot study in which 16 asymptomatic CRPC patients with low to moderate metastatic burden were treated with testosterone cypionate (400 mg intramuscular; day 1 of 28) and etoposide (100 mg oral daily; days 1 to 14 of 28). After three cycles, those with a declining prostate-specific antigen (PSA) continued on intermittent testosterone therapy monotherapy. Castrating therapy was continued to suppress endogenous testosterone production, allowing for rapid cycling from supraphysiologic to near-castrate serum testosterone levels, a strategy termed bipolar androgen therapy (BAT). BAT was well tolerated and resulted in high rates of PSA (7 of 14 evaluable patients) and radiographic responses (5 of 10 evaluable patients). Although all men showed eventual PSA progression, four men remained on BAT for ≥1 year. All patients (10 of 10) demonstrated PSA reductions upon receiving androgen-ablative therapies after BAT, suggesting that BAT may also restore sensitivity to ADTs. BAT shows promise as treatment for CRPC and should be further evaluated in larger trials.
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