Is leflunomide (a disease-modifying antirheumatic drug (DMARD)) used as a last-line treatment in metastatic prostate cancer?

From the Guidelines

No, leflunomide is not considered a last ditch effort in metastatic prostate cancer. Leflunomide is primarily an immunomodulatory drug approved for rheumatoid arthritis treatment, marketed under brand names like Arava, typically dosed at 10-20mg daily. It has not been established as a standard treatment option for metastatic prostate cancer in clinical practice. The standard treatments for metastatic prostate cancer include androgen deprivation therapy (ADT), newer anti-androgens like enzalutamide or apalutamide, chemotherapy agents such as docetaxel or cabazitaxel, and targeted therapies like PARP inhibitors for specific genetic mutations. While some preclinical research has explored leflunomide's potential anti-cancer properties through its inhibition of dihydroorotate dehydrogenase (DHODH) and effects on cell proliferation, this has not translated into approved clinical applications for prostate cancer. Patients with metastatic prostate cancer should discuss established treatment options with their oncologists rather than considering leflunomide as a treatment approach, as recommended by recent guidelines such as the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer 1.

Some key points to consider in the management of metastatic prostate cancer include:

• The use of androgen deprivation therapy (ADT) with treatment intensification for patients with metastatic castration-sensitive prostate cancer 1
• The role of newer anti-androgens, chemotherapy agents, and targeted therapies in the treatment of metastatic prostate cancer 1
• The importance of shared decision-making between patients and their oncologists in selecting the most appropriate treatment approach 1
• The need for ongoing monitoring and adjustment of treatment plans as needed to optimize patient outcomes 1

Overall, the management of metastatic prostate cancer requires a comprehensive and multidisciplinary approach, and patients should discuss their treatment options with their oncologists to determine the best course of care.

From the Research

Treatment Options for Metastatic Prostate Cancer

• The standard treatment for metastatic prostate cancer has evolved, with high-level evidence supporting upfront combination therapy with either docetaxel or new hormonal agents, resulting in improved overall survival for patients with metastatic hormone-sensitive prostate cancer 2.
• Systemic treatment of men with metastatic prostate cancer is rapidly evolving, with androgen deprivation therapy remaining the first-line treatment for advanced disease, and the addition of docetaxel markedly improving survival in patients with extensive metastatic disease 3.
• First-line treatment options for patients with metastatic prostate cancer include androgen suppression, with goserelin therapy appearing to have similar efficacy to orchiectomy in terms of survival 4.
• Novel hormonal agents, such as abiraterone and enzalutamide, have been shown to be active in second-line or subsequent hormonal therapy for castration-resistant prostate cancer, and recent data have shown a substantial anticancer effect in initial therapy 5.

Use of Leflunomide in Metastatic Prostate Cancer

• There is no mention of leflunomide, a disease-modifying antirheumatic drug (DMARD), being used as a treatment option for metastatic prostate cancer in the provided studies.
• The studies focus on androgen deprivation therapy, docetaxel, and novel hormonal agents as treatment options for metastatic prostate cancer, with no reference to leflunomide 2, 3, 4, 5, 6.