Is Lifulo associated with a history of prostate cancer?

Lifulo (Relugolix) in Patients with History of Prostate Cancer

Lifulo (relugolix) is not contraindicated in patients with a history of prostate cancer; in fact, it is specifically indicated for the treatment of advanced hormone-sensitive prostate cancer.

Mechanism and Indications

Relugolix (Lifulo) is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist that works by directly blocking GnRH receptors, leading to rapid suppression of testosterone production. Unlike traditional luteinizing hormone-releasing hormone (LHRH) agonists such as leuprolide, relugolix:

• Achieves rapid testosterone suppression without the initial testosterone surge
• Provides sustained testosterone suppression to castrate levels
• Allows for faster testosterone recovery upon discontinuation 1

Evidence for Use in Prostate Cancer

The HERO trial demonstrated that relugolix was superior to leuprolide in achieving and maintaining testosterone suppression in men with advanced prostate cancer:

• 96.7% of men receiving relugolix maintained castration through 48 weeks compared to 88.8% with leuprolide
• Relugolix achieved castrate levels of testosterone by day 4 in 56% of patients, compared to 0% with leuprolide
• Relugolix showed a 54% lower risk of major adverse cardiovascular events compared to leuprolide 1

Clinical Applications

Relugolix is specifically indicated for:

• Advanced hormone-sensitive prostate cancer
• Neo-adjuvant and adjuvant treatment in combination with radiotherapy for high-risk localized or locally advanced hormone-dependent prostate cancer 2

Combination Therapy

Relugolix can be effectively combined with other prostate cancer treatments:

• Case reports show successful use of relugolix plus enzalutamide in metastatic hormone-sensitive prostate cancer
• This combination has demonstrated sustained PSA reduction and good tolerability 2

Advantages Over Injectable LHRH Agonists

Relugolix offers several advantages over traditional injectable therapies like leuprolide:

1. Oral administration (once daily dosing)
2. No testosterone flare that could worsen symptoms
3. Rapid onset of action
4. Lower risk of cardiovascular events
5. Faster testosterone recovery upon discontinuation 1

Monitoring Recommendations

For patients with a history of prostate cancer taking relugolix:

• Regular PSA monitoring
• Testosterone level assessment to confirm adequate suppression
• Cardiovascular risk assessment
• Monitoring for common side effects including hot flashes and fatigue

Special Considerations

The NCCN guidelines emphasize that patients with a history of prostate cancer require careful monitoring, regardless of the treatment approach. This includes regular PSA testing and digital rectal examination 3.

For patients with genetic predisposition to prostate cancer (such as Li-Fraumeni syndrome), annual PSA testing and digital rectal examination starting at age 35 is recommended 3.

Conclusion

Relugolix represents an important therapeutic option for patients with advanced prostate cancer, offering advantages over traditional injectable therapies in terms of administration, safety profile, and rapid onset/offset of action. Its use should be guided by the specific characteristics of the patient's prostate cancer and treatment goals.