apalutamidi

Apalutamidi, also known as apalutamide, is a non-steroidal antiandrogen used in the treatment of prostate cancer. It is approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) and, in combination with androgen-deprivation therapy (ADT), for metastatic castration-sensitive prostate cancer (mCSPC). Regulators in several regions have sanctioned its use based on trials showing delayed disease progression and improved survival in these settings.

Mechanism of action: Apalutamidi binds to the ligand-binding domain of the androgen receptor (AR) and functions as an antagonist/inverse agonist. By blocking AR signaling, it inhibits AR-driven gene expression and tumor cell proliferation. Resistance can develop through AR amplification, mutations, or splice variants, or via activation of alternative growth pathways.

Administration and pharmacokinetics: The drug is taken orally as a tablet, typically 240 mg once daily, with or without food. It has active metabolites and a relatively long half-life, which leads to gradual achievement of steady-state drug levels over several weeks.

Adverse effects and safety: Common adverse effects include fatigue, rash (often mild to moderate), hypothyroidism, hot flashes, diarrhea, nausea, back pain, and weight loss. Falls and fractures have been reported in some patients. Rare but serious events include severe skin reactions and seizures; appropriate monitoring is advised. Drug interactions primarily involve the cytochrome P450 system, particularly CYP3A4 inhibitors or inducers, which can affect apalutamide levels. The drug is contraindicated during pregnancy due to risk to the fetus.

Regulatory status and history: Developed by Janssen, apalutamidi has been approved by major regulatory authorities for nmCRPC and mCSPC and is incorporated into guidelines as a standard treatment option in appropriate patients.