Rucaparib
Indications
Rucaparib is used for:
Ovarian Cancer
Adult Dose
Ovarian Cancer
Indicated as monotherapy for patients with deleterious BRCA mutation (germline and/or somatic) associated with advanced ovarian cancer who have been treated with >2 chemotherapies
Also, indicated for the maintenance treatment of recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy
Initial dose: 600 mg (two 300 mg tablets) PO BID
Continue treatment until disease progression or unacceptable toxicity
Hepatic impairment
Mild (total bilirubin ?upper limit of normal [ULN] and AST >ULN, or total bilirubin between 1-1.5x ULN and any AST): No dose adjustment required
Moderate-to-severe (total bilirubin >1.5x ULN): Lack of data; no recommendation available
Child Dose
Renal Dose
Renal impairment
Mild-to-moderate (CrCl 30-89): No dose adjustment required
Severe (CrCl <30 mL/min) or patients on dialysis: Lack of data; no recommendation available
Administration
May administer with or without food
Contra Indications
Precautions
Rare reports of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML); measure CBC at baseline and monthly thereafter; do not initiate until patients recover from hematological toxicities caused by previous chemotherapy (ie, ≤grade 1); also see Dosage Modifications
Increases susceptibility to sunburn; advise patients to use appropriate sun protection
Based on its mechanism of action, can cause fetal harm
Pregnancy-Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women
There are no available data in pregnant women to inform the drug-associated risk
Pregnancy testing recommended for females of reproductive potential before initiating
Advise women to use effective contraception during treatment and for 6 months following the final dose
Lactation
Unknown if distributed in human breast milk
Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for 2 weeks after the final dose
Interactions
Adverse Effects
Side effects of Rucaparib :
>10%
Increased creatinine (98%)
Decreased hemoglobin (88%)
Increased cholesterol (84%)
Nausea (76-77%)
Asthenia/fatigue (73-77%)
Increased AST/ALT (38-73%)
Vomiting (46%)
Abdominal pain/distension (46%)
Decreased lymphocytes (45%)
Decreased platelets (44%)
Decreased leukocytes (44%)
Anemia (39-44%)
Rash (43%)
Constipation (37-40%)
Decreased appetite (23-39%)
Decreased neutrophils (38%)
Increased alkaline phosphatase (37%)
Dysgeusia (40%)
Decreased ANC (35%)
Diarrhea (32%)
Abdominal pain (32%)
Thrombocytopenia (21-29%)
Decreased lymphocytes (29%)
Nasopharyngitis/upper respiratory tract infection (29%)
Stomatitis (28%)
Anemia, grades 3-4 (21%)
Dyspnea (21%)
Neutropenia (20%)
Dizziness (17%)
Decreased hemoglobin, grades 3-4 (13%)
Increased AST/ALT, grades 3-4 (1-11%)
Pyrexia (11%)
1-10%
Photosensitivity (10%)
Decreased ANC, grades 3-4 (10%)
Pruritus (9%)
Decreased lymphocytes, grades 3-4 (7%)
Asthenia/fatigue, grades 3-4 (7%)
Decreased neutrophils, grades 3-4 (6%)
Decreased lymphocytes, grades 3-4 (6%)
Thrombocytopenia, grades 3-4 (5%)
Vomiting, grades 3-4 (4%)
Increased cholesterol, grades 3-4 (4%)
Nausea, grades 3-4 (4%)
Abdominal pain, grades 3-4 (3%)
Decreased appetite, grades 3-4 (3%)
Decreased leukocytes, grades 3-4 (3%)
Palmar-plantar erythrodysesthesia syndrome (2%)
Constipation, grades 3-4 (2%)
Diarrhea, grades 3-4 (2%)
Decreased platelets, grades 3-4 (2%)
Febrile neutropenia (1%)
<1%
Dyspnea, grades 3-4 (0.5%)
Dysgeusia, grades 3-4 (0.3%)
Increased creatinine, grades 3-4 (0.3%)
Mechanism of Action
Inhibitor of poly (ADP-ribose) polymerase (PARP) enzymes, including PARP-1, PARP-2, and PARP-3, which play a role in DNA repair
In vitro studies have shown that rucaparib-induced cytotoxicity may involve inhibition of PARP enzymatic activity and increased formation of PARP-DNA complexes resulting in DNA damage, apoptosis, and cell death
Increased rucaparib-induced cytotoxicity was observed in tumor cell lines with deficiencies in BRCA1/2 and other DNA repair genes
Rucaparib has been shown to decrease tumor growth in mouse xenograft models of human cancer with or without deficiencies in BRCA