Rucaparib

Rucaparib, sold under the brand name Rubraca, is an oral small-molecule inhibitor of the poly(ADP-ribose) polymerase (PARP) enzymes, primarily PARP1 and PARP2. By inhibiting PARP in tumor cells with BRCA1/2 or other homologous recombination deficiencies, rucaparib increases DNA damage and promotes cancer cell death through synthetic lethality.

Rucaparib is approved for several indications in adults. It is used for the treatment of deleterious BRCA mutation-associated ovarian cancer following prior platinum-based chemotherapy, as maintenance therapy in recurrent ovarian cancer that has responded to platinum therapy, and for deleterious BRCA mutation-associated metastatic castration-resistant prostate cancer. These approvals reflect its role as a targeted therapy for tumors with homologous recombination repair defects.

Administration and dosing are oral. The typical dose is 600 mg taken twice daily, with or without food, and adjustments may be made for hematologic toxicity or organ impairment. The drug is primarily metabolized in the liver and eliminated via urine and feces; its half-life is on the order of about a day. Coadministration with strong inhibitors or inducers of cytochrome P450 enzymes may necessitate dose adjustments. Use in pregnancy is contraindicated; effective contraception should be used during treatment.

Common adverse effects include anemia and thrombocytopenia, nausea, fatigue, elevated liver enzymes, vomiting, and decreased appetite. Monitoring typically includes regular blood counts and liver function tests, along with assessment for signs of hematologic toxicity. Drug interactions can occur with other anticancer agents and with strong CYP inhibitors or inducers.

Rucaparib was developed by Clovis Oncology and received FDA approval in 2016, with subsequent authorizations expanding its use in ovarian maintenance and BRCA-mutated metastatic prostate cancer.