Abiraterone acetate (AA), a drug that inhibits CYP17A1 to suppress androgen production, is a standard treatment, typically given as a 1000 mg daily dose on an empty stomach with prednisone or prednisolone. However, its high cost limits access, especially in resource-constrained regions. A recent study published in Cancer Communications  investigates a model-informed 500 mg daily dose of AA taken with a low-fat meal, showing it may offer comparable efficacy and safety at a reduced cost, potentially transforming prostate cancer care.

Conducted at two Singapore hospitals, the prospective, single-arm trial enrolled 9 Asian men with metastatic prostate cancer (28% mCSPC, 22% mCRPC). Patients received 500 mg AA daily with a low-fat meal (7–15 g fat) for 12 weeks, alongside 5 mg prednisone twice daily (mCRPC) or 5 mg prednisolone daily (mCSPC).
The study evaluated efficacy through CYP17A1 inhibition (measured by testosteroneilya testosterone and androstenedione levels), PSA response, pharmacokinetics (PK), and safety.

The rationale for the low-dose regimen stems from AA’s increased bioavailability with food, which could allow a reduced dose to achieve similar drug exposure as the 1000 mg fasted dose.

All individuals showed a decline in PSA levels by week 12 of treatment with low-dose abiraterone (500 mg daily).
A ≥50% PSA decline at any time point was observed in 78% of patients.
Among the mHSPC group, six patients experienced a ≥50% decline by week 4, which deepened to ≥80% by week 12.

Of the two mCRPC patients, one achieved a 91.1% PSA decline at week 12, while the other showed a 90.4% decline at week 8 followed by a rebound to 22.1% at week 12, potentially due to an ATM gene mutation known to impair responses to androgen receptor-targeted therapies.

The treatment was well tolerated, with adverse events reported in six patients; hypokalemia was the most common, aligning with previous findings, and no other notable AEs were observed. Baseline levels of testosterone, androstenedione, DHEA-S, and cortisol were similar across both patient groups, with testosterone levels in the castrate range (median 14.62 ng/dL). From the first visit onward, all four hormones declined substantially and in parallel, indicating effective endocrine suppression by the low-dose regimen. Pharmacokinetic and pharmacodynamic modeling confirmed that CYP17A1 enzyme occupancy remained above 80% despite a 50% reduction in systemic abiraterone exposure compared to the standard 1,000 mg dose, and enzyme inhibition persisted due to slow release from tight drug binding. Overall, the findings support the biological and clinical effectiveness of 500 mg abiraterone in both mHSPC and mCRPC settings.

The safety profile was similar to or better than historical 1000 mg dose data.

PARAMETER	Details
Number of patients	9 (7 mHSPC, 2 mCRPC)
PSA decline at week 12	Observed in all 9 patients
PSA ≥ 50% decline (any visit)	7 of 9 patients (78%)
PSA response in mHSPC patients	6 patients had ≥ 50% decline at week 4; ≥ 80% at week 12
PSA response in mCRPC patients	– 1 patient: 91.1% decline at week 12 – 1 patient: 90.4% decline at week 8, rebound to 22.1% at week 12 (ATM mutation present)
Safety (AEs)	– AEs in 6 of 9 patients – Most common AE: hypokalemia – No other reported AEs observed
Baseline hormone levels	Testosterone, androstenedione, DHEA-S, cortisol similar in mHSPC and mCRPC; median testosterone = 14.62 ng/dL
Hormonal suppression	Substantial and well-correlated suppression of all 4 steroids from Visit 1
Pharmacodynamics modeling	– CYP17A1 occupancy > 80% at 500 mg AA – Effect persists despite 50% lower systemic exposure vs. 1,000 mg AA – Free CYP17A1 released slowly after drug clearance

Source.