Lower dose of abiraterone shows comparable efficacy to standard dose for prostate cancer

A lower dose of abiraterone acetate (AA; Zytiga; 500 mg) demonstrated promise in delivering optimal anti-tumor efficacy and a favorable safety profile compared with the standard 1000-mg dose in the treatment of patients with prostate cancer, according to data from a phase 1 study published in Cancer Communications.¹

“Our findings open the door to more cost-effective and safer treatment for prostate cancer patients, with minimal compromise on efficacy,” said Eric Chan, PhD, and Edmund Chiong, MBBS, PhD, FRCSEd, FRCSI, FAMS (Urology), in a news release on the study results.²

These data build off prior working from a global phase 2 trial showing that a 250 mg dose of AA taken with a low-fat meal achieved comparable prostate-specific antigen (PSA) metrics compared with the standard AA dose in a fasting state among patients with castration-resistant prostate cancer (CRPC). However, the authors noted that ensuring patient compliance with a low-fat diet may pose challenges, and thus further determined that a 500-mg dose of AA in a fasted state demonstrated comparable pharmacokinetic (PK) data to the 250-mg dose with a low-fat meal.

The authors added, “Furthermore, our modeling studies revealed that 500-mg AA is promising in achieving optimal antitumor efficacy and diminishing mineralocorticoid-related adverse outcomes simultaneously. In addition, patients will pay less with a half-reduced dose. Currently, data on the administration of 500-mg AA in prostate cancer patients remains insufficient.”

To that end, the investigators conducted a proof-of-concept phase 1 study assessing the efficacy and safety of a 500 mg once-daily AA dose in 2 patients with metastatic CRPC (mCRPC) and 7 patients with metastatic hormone-sensitive prostate cancer (mHSPC). The median age of patients was 72 years (range, 65 to 90).

Patients in the study received 500 mg of AA once daily for 12 weeks plus oral prednisolone 5 mg twice daily for mCRPC and 5 mg once daily for mHSPC. The authors added, “After this period, patients were reverted to the standard 1000 mg dose due to ethical considerations and were followed up with routine clinical visits.”

Overall, data showed that all 9 patients achieved a decline in PSA level by week 12. Further, 78% of patients (7 of 9) achieved a PSA decline of at least 50% at any visit. Six patients with mHSPC achieved a PSA decline of at least 50% by week 4, which further decreased to at least 80% at week 12.

The authors also reported, “24-h PK profiles revealed that the systemic exposure of 500-mg AA was comparable with previous results from mCRPC patients under the same dose and was approximately half of that previously observed or simulated with a 1000 mg dose of AA.”

Low dose AA also showed substantial suppression of testosterone, androstenedione, DHEA-S and cortisol, which “support[s] the pharmacological response of 500-mg AA,” according to the authors.

Further, treatment with the lower-dose regimen maintained CYP17A1 enzyme occupancy at over 80% despite the 50% reduction in systemic exposure to AA.

The lower dose of AA was also shown to be safe and well-tolerated. In total, 6 of 9 patients experienced an adverse event (AEs) of any cause during the 12-week treatment period. The most common AE was hypokalemia. Other AEs included dry throat, weight gain, puffiness of face, and hot flushes. Notably, other reported AEs were not observed in the current study.

Based on these findings, the authors concluded, “Our proof-of-concept phase I study and PBPK/PD modeling results underscored the pharmacological response of the low-dose regimen, and were consistent with our hypothesis that a lower dose of AA is promising for achieving optimal antitumor efficacy, reducing adverse outcomes, and alleviating financial burdens simultaneously. A long-term, large-scale, controlled clinical trial is essential to further evaluate and confirm the clinical efficacy of low-dose AA therapy.”

REFERENCES

1. Chiong E, Wang Z, Cheong EJY, et al. Evaluation of exposure-response-safety relationship of model-informed low-dose 500 mg abiraterone acetate in prostate cancer patients. Cancer Commun (Lond). 2025. doi:10.1002/cac2.70035

2. Lower dose of abiraterone acetate as effective for prostate cancer treatment. News release. National University of Singapore. July 23, 2025. Accessed July 29, 2025. https://www.eurekalert.org/news-releases/1092211