|By mouth (tablets)|
|Bioavailability||30–45% (Tmax = 1.9 hours)|
|Protein binding||70% (in vitro)|
|Metabolism||Liver (primarily CYP2D6; 1A2 and 3A4 to a lesser extent)|
|Elimination half-life||17–19 hours|
|Chemical and physical data|
|Molar mass||323.371 g·mol−1|
|3D model (JSmol)|
The most common side effects include tiredness or weakness, nausea (feeling sick), increased levels of creatinine (which may indicate kidney problems) and liver enzymes in the blood (which may indicate liver damage), vomiting, anaemia (low red blood cell counts), decreased appetite, dysgeusia (taste disturbances), diarrhoea, thrombocytopenia (low levels of platelets) and abdominal pain (belly ache). It is a PARP inhibitor. Rucaparib is a first-in-class pharmaceutical drug targeting the DNA repair enzyme poly-ADP ribose polymerase-1 (PARP-1).
Rucaparib is approved for medical use in the United States and Europe.
Rucaparib is indicated as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy.
Rucaparib is indicated as monotherapy treatment of adults with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum based chemotherapy, and who are unable to tolerate further platinum based chemotherapy.
Mechanism of action
Rucaparib inhibits "the contraction of isolated vascular smooth muscle, including that from the tumours of cancer patients. It also reduces the migration of some cancer and normal cells in culture."
It was discovered as part of a collaboration between scientists working at the Northern Institute of Cancer Research and Medical School of Newcastle University and Agouron Pharmaceuticals in San Diego, California. It is being developed by Clovis Oncology.
In the European Union it was designated an orphan medicinal product on 10 October 2012. On 22 March 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorisation, intended for the treatment of relapsed or progressive ovarian cancer. It was approved for medical use in the European Union in May 2018.
After the FDA approval, TRITON2 and TRITON3 mCRPC studies were initiated in order to determine how patients with prostate cancer will respond to the rucaparib drug. The studies for these two trials are still going on and the estimated dates for the first results are range between 2019 and 2022.
The ARIEL3 and ARIEL4 are two randomized, double-blind phase III studies. The ARIEL3 study was designed to evaluate the effect of the investigational agent as a maintenance treatment for the advanced platinum-sensitive ovarian cancer patients compared placebo after their response to at least two prior chemotherapies. The top-line results from the study were presented at the ESMO 2017 congress and right after that, it was published in the Lancet journal in September 2017. The findings showed significant improvement in progression-free survival (PFS) in patients treated with Rubraca than placebo. Recently, in October 2017, a supplemental sNDA for the rucaparib ARIEL3 maintenance treatment has been submitted to the FDA.
The ARIEL4 trial is still ongoing[when?] to evaluate how patients will best respond to treatment with rucaparib compared with chemotherapy. The estimated data collection date for primary outcome measurement will be in June 2022.
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