Rucaparib
Overview
Rucaparib is an oral poly (ADP-ribose) polymerase (PARP) inhibitor used in targeted cancer therapy, particularly for tumors with BRCA1/2 mutations or homologous recombination deficiency (HRD). It is approved for the treatment of certain advanced ovarian, fallopian tube, and primary peritoneal cancers, as well as metastatic castration-resistant prostate cancer (mCRPC). By blocking PARP enzymes, rucaparib prevents DNA repair in cancer cells, leading to cell death while sparing most normal cells. It is generally prescribed for patients who have received prior chemotherapy or targeted therapy, and is also used in maintenance settings to prolong remission following platinum-based chemotherapy. The drug is taken orally, offering convenience and flexibility for long-term cancer management.
Background and Date of Approval
Rucaparib was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2016 for advanced ovarian cancer in patients with deleterious BRCA mutations after at least two prior chemotherapies. Subsequent approvals expanded its use to maintenance treatment for recurrent ovarian, fallopian tube, or primary peritoneal cancers responding to platinum-based chemotherapy. In May 2020, it was approved for mCRPC with deleterious BRCA mutations following androgen receptor–directed therapy and taxane chemotherapy. The European Medicines Agency (EMA) and other regulators have authorized rucaparib for similar indications. Clinical trials such as ARIEL2 and ARIEL3 demonstrated its efficacy in improving progression-free survival in HRD-positive tumors.
Uses
Rucaparib is indicated for the maintenance treatment of adults with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy. It is also approved for adult patients with deleterious germline or somatic BRCA mutation–positive mCRPC after treatment with androgen receptor–directed therapy and taxane-based chemotherapy. Off-label, it may be considered in select HRD-positive cancers based on clinical evidence and patient genetics.
Administration
Rucaparib is administered orally at a recommended dose of 600 mg twice daily, with or without food. Treatment is continued until disease progression or unacceptable toxicity. Dose reductions may be required for adverse reactions, and therapy should be interrupted or adjusted in cases of severe hematologic or hepatic toxicity. Blood counts and liver function should be monitored regularly.
Side Effects
The most frequently reported side effects include nausea, vomiting, fatigue, anemia, thrombocytopenia, decreased appetite, constipation, diarrhea, and altered taste. Most effects are mild to moderate, but medical advice should be sought if symptoms worsen or persist.
Warnings
Serious risks include myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), severe bone marrow suppression, and significant liver enzyme elevations. Rucaparib is contraindicated in patients with hypersensitivity to the drug or its excipients. Pregnancy and breastfeeding should be avoided due to potential fetal harm.
Precautions
Caution is advised in patients with pre-existing bone marrow suppression or liver disease. Rucaparib may interact with drugs metabolized by certain cytochrome P450 enzymes. Strong CYP inhibitors or inducers may alter its plasma levels and require monitoring. Effective contraception should be used during treatment and for six months after the last dose.
Expert Tips
Ensure genetic testing for BRCA or HRD status before initiating therapy. Counsel patients on the importance of adherence to the dosing schedule. Monitor complete blood counts and liver function tests periodically. Advise patients to report signs of infection, unusual bruising, or prolonged fatigue promptly. Encourage hydration and small, frequent meals to reduce nausea.