- Class: PARP inhibitor (Poly (ADP-ribose) polymerase inhibitor)
- Mechanism of Action: Inhibits PARP-1 and PARP-2 enzymes, preventing repair of single-strand DNA breaks. In tumors with homologous recombination deficiency (e.g., BRCA mutations), this leads to accumulation of DNA damage and cancer cell death (synthetic lethality).
Indications
- Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.
- Also approved for maintenance therapy regardless of biomarker status (BRCA mutation or homologous recombination deficiency).
- Approved for maintenance treatment in HRR (homologous recombination repair)-deficient metastatic castration-resistant prostate cancer (mCRPC) after response to prior therapy.
Dosage
- Starting dose:
- Typically 300 mg orally once daily, taken continuously.
- Dose can be adjusted based on body weight (<77 kg) or platelet count (<150,000/mm³) to reduce risk of hematologic toxicity.
- Absorption: Oral; peak concentration ~3 hours.
- Metabolism: Primarily by carboxylesterases, minor by CYP enzymes.
- Half-life: ~36 hours.
- Elimination: Mainly fecal and urinary.
Key Toxicities and Monitoring
- Common adverse effects:
- Hematologic toxicity: thrombocytopenia, anemia, neutropenia
- Fatigue, Nausea, Hypertension, Insomnia
- Serious risks:
- Myelodysplastic syndrome/acute myeloid leukemia (rare)
- Hypertension and cardiovascular events
- Monitoring:
- CBC regularly to monitor blood counts.
- Blood pressure monitoring.
- Liver and renal function tests as indicated.
Drug Interactions: No significant CYP3A4 interactions, but caution with other myelosuppressive agents.