Search. Learn. Save

Platform for Pharmaceutical Products for Healthcare Professionals
Search By
☰ Generic Formulas

Generic Formulas X

Abiraterone Acetate

Abiraterone Acetate: A Game-Changer in Prostate Cancer Therapy

Introduction

Prostate cancer remains one of the most commonly diagnosed cancers among men worldwide. While early-stage disease is often curable, advanced or metastatic prostate cancer poses significant challenges in management. Over the past few decades, the understanding of prostate cancer biology has driven innovations in targeted therapy—one of the most impactful being Abiraterone Acetate, a selective androgen biosynthesis inhibitor. First approved in 2011 for metastatic castration-resistant prostate cancer (mCRPC), Abiraterone Acetate (marketed as Zytiga) has significantly extended survival in patients and transformed the standard of care. In this blog, we will explore the pharmacology, clinical application, therapeutic potential, and safety considerations of this life-extending medication.

The Role of Androgens in Prostate Cancer

To understand the significance of Abiraterone, it's crucial to appreciate how prostate cancer progresses.

Androgens—primarily testosterone and dihydrotestosterone (DHT)—are key drivers of prostate cancer growth. These hormones bind to androgen receptors in prostate cells, promoting proliferation and survival. In most cases, prostate cancer is initially androgen-sensitive, meaning that reducing androgen levels can inhibit tumor growth.

This principle forms the basis of androgen deprivation therapy (ADT), commonly involving surgical or chemical castration. However, many patients eventually develop castration-resistant prostate cancer (CRPC), a form of the disease that continues to progress despite low testosterone levels.

This is where Abiraterone Acetate enters the picture.

Abiraterone Acetate

Abiraterone Acetate is a prodrug of Abiraterone, a selective and irreversible inhibitor of the enzyme CYP17A1 (17α-hydroxylase/C17,20-lyase). This enzyme is critical in the biosynthesis of androgens not only in the testes but also in the adrenal glands and even within the tumor microenvironment.

By inhibiting CYP17A1, Abiraterone effectively suppresses androgen production from all sources, offering a more complete androgen blockade than traditional ADT alone.

Mechanism of Action

Inhibition of CYP17A1

CYP17A1 catalyzes two key reactions in the androgen synthesis pathway:

  1. 17α-hydroxylation of pregnenolone and progesterone.

  2. Conversion of these hydroxylated products to dehydroepiandrosterone (DHEA) and androstenedione.

These are precursors to testosterone and DHT.

By blocking this enzyme, Abiraterone depletes systemic and intratumoral androgen levels to undetectable concentrations, starving the cancer cells of the growth signals they need to survive.

Consequences of CYP17A1 Inhibition

While this mechanism is effective, it also disrupts glucocorticoid and mineralocorticoid balance, leading to:

  • Corticosteroid deficiency: Decreased cortisol production.

  • Mineralocorticoid excess: Increased levels of aldosterone-like activity, causing hypertension, fluid retention, and hypokalemia.

To counteract this, prednisone is co-administered with Abiraterone to replace cortisol and suppress ACTH stimulation.

Pharmacokinetics

  • Absorption: Oral bioavailability improves with a high-fat meal (but it is advised to take it on an empty stomach).

  • Metabolism: Hepatically metabolized via CYP3A4 and SULT2A1.

  • Elimination: Primarily excreted via feces.

  • Half-life: 12 ± 5 hours.

Indications for Use

1. Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Approved for use in patients who have either:

  • Received prior chemotherapy (e.g., docetaxel), or

  • Are chemotherapy-naïve but show progression on ADT.

Abiraterone plus prednisone improves overall survival (OS) and radiographic progression-free survival (rPFS) in these populations.

2. Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

Following studies like LATITUDE and STAMPEDE, Abiraterone is now also approved in combination with ADT for high-risk metastatic hormone-sensitive prostate cancer, demonstrating substantial improvements in survival and quality of life.

3. Non-metastatic CRPC (off-label/in trials)

Explored in patients with biochemical recurrence or high PSA but no radiologic metastases, although not a standard of care in these cases yet.

Key Clinical Trials

1. COU-AA-301 (Post-Chemotherapy mCRPC)

  • Design: Phase III, Abiraterone + prednisone vs. placebo + prednisone.

  • Outcome: Median OS improved by 4.6 months (14.8 vs. 10.2 months).

  • Conclusion: Confirmed benefit in patients previously treated with docetaxel.

2. COU-AA-302 (Chemotherapy-Naïve mCRPC)

  • Design: Phase III, Abiraterone + prednisone vs. placebo.

  • Outcome: Significant delay in radiographic progression and time to pain progression.

  • Conclusion: Abiraterone effective before chemotherapy.

3. LATITUDE Trial (mCSPC)

  • Design: Abiraterone + prednisone + ADT vs. ADT alone.

  • Outcome: OS benefit (not reached vs. 34.7 months at analysis).

  • Conclusion: Established Abiraterone as first-line treatment for high-risk mCSPC.

Administration and Dosage

  • Typical dose: 1000 mg (four 250 mg tablets) orally once daily.

  • With prednisone: 5 mg orally twice daily.

  • On an empty stomach: At least 1 hour before or 2 hours after meals.

Newer formulations, such as 500 mg tablets and combinations with other drugs (e.g., Abiraterone + apalutamide), are also available for convenience and improved compliance.

Side Effects and Safety Profile

Common Adverse Effects

  • Fatigue

  • Hypertension

  • Hypokalemia

  • Edema

  • Hot flashes

  • Diarrhea

Mineralocorticoid-Related Toxicities

Due to elevated ACTH and aldosterone levels:

  • Fluid retention

  • Hypertension

  • Low potassium

Management includes:

  • Co-administration of prednisone,

  • Monitoring of blood pressure and electrolytes,

  • Diuretics or mineralocorticoid receptor antagonists (e.g., eplerenone) if needed.

Hepatotoxicity

  • Elevation of liver enzymes (ALT/AST) may occur.

  • Liver function should be monitored before and during treatment.

Cardiac Risk

  • Caution in patients with a history of cardiovascular disease.

  • Monitoring for signs of arrhythmias or fluid overload is recommended.

Drug Interactions

Abiraterone is metabolized by CYP3A4, and also inhibits CYP2D6 and CYP2C8, leading to potential interactions with:

  • Anticoagulants (e.g., warfarin),

  • Antidepressants,

  • Antiepileptics,

  • Other hormone therapies.

Avoid strong CYP3A4 inducers like rifampin and carbamazepine.

Abiraterone vs. Enzalutamide

Another key therapy in prostate cancer is Enzalutamide, an androgen receptor inhibitor. While both drugs improve survival, they differ in mechanism and side effect profiles.

Feature Abiraterone Enzalutamide
Mechanism Inhibits androgen synthesis Blocks androgen receptor
Requires corticosteroids Yes (prednisone) No
Risk of seizures Low Higher (caution in seizure-prone)
Fatigue Moderate Higher
Cardiovascular effects Yes Less pronounced

Choice depends on patient-specific factors, such as comorbidities, prior treatment, and tolerance.

Cost and Accessibility

Abiraterone is considered a high-cost medication, particularly in countries without universal healthcare. Generic versions have become available in many regions, lowering cost burdens.

Access programs and insurance coverage vary widely, making financial counseling an important part of prostate cancer management.

Real-World Impact

Since its approval, Abiraterone has been prescribed to hundreds of thousands of patients globally. Its real-world data mirror clinical trial outcomes, with consistent improvements in:

  • Time to progression,

  • Overall survival,

  • Delay in symptomatic deterioration.

It also offers a more tolerable alternative to chemotherapy in many settings, especially for elderly or frail patients.

Future Directions and Combinations

1. Earlier Use in Localized Disease

Trials are ongoing to assess Abiraterone in:

  • High-risk localized disease (as neoadjuvant therapy),

  • Adjuvant settings post-prostatectomy or radiotherapy.

2. Combinations with Other Agents

  • PARP inhibitors (e.g., olaparib) for patients with DNA repair gene mutations,

  • Immunotherapy (e.g., checkpoint inhibitors),

  • Chemohormonal therapy for aggressive disease.

3. Biomarker-Guided Therapy

Researchers are exploring AR-V7 status, circulating tumor DNA, and genetic profiling to predict response and resistance to Abiraterone.

Conclusion

Abiraterone Acetate has redefined the therapeutic landscape for advanced prostate cancer, offering a powerful weapon in the fight against androgen-driven tumor growth. By targeting androgen biosynthesis at its root, it achieves comprehensive hormonal suppression, delaying progression and improving survival.

Though associated with potential side effects—particularly those related to mineralocorticoid excess—these are manageable with proper monitoring and supportive care. As research continues, Abiraterone's role is expanding beyond late-stage disease into earlier phases and combination regimens, with the promise of even greater impact.

For clinicians and patients navigating the complexities of advanced prostate cancer, Abiraterone represents a beacon of hope and a testament to the power of targeted therapy.

References

  1. de Bono JS, et al. "Abiraterone and increased survival in metastatic prostate cancer." NEJM, 2011.

  2. Fizazi K, et al. "Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer." NEJM, 2017.

  3. Ryan CJ, et al. "Abiraterone in metastatic prostate cancer without previous chemotherapy." NEJM, 2013.

  4. U.S. FDA. “Zytiga Prescribing Information.”

  5. James ND, et al. "Addition of abiraterone to standard of care in men with locally advanced or metastatic prostate cancer: STAMPEDE trial." Lancet, 2017.