title: Olaparib for the treatment of BRCA-mutated advanced ovarian cancer.
abstract: OBJECTIVE
  The pharmacology, clinical efficacy, safety, dosage and administration, and role in therapy of olaparib, a first-in-class treatment for advanced treatment-refractory ovarian cancer, are reviewed.
  
  
  CONCLUSIONS
  Olaparib (Lynparza, AstraZeneca) is an oral inhibitor of poly(ADP-ribose) polymerase (PARP) proteins that play a key role in DNA repair and genomic stability. Olaparib is indicated for use in treating certain patients with advanced, recurrent ovarian cancer who have mutations of the breast cancer 1 gene (BRCA1) or breast cancer 2 gene (BRCA2). In patients with BRCA-mutated cancers, olaparib blocks vital PARP-mediated tumor cell DNA repair mechanisms, leading to "synthetic lethality" and selective tumor cell death. In Phase II clinical trials including patients with platinum-sensitive, platinum-resistant, and platinum-refractory ovarian cancers, olaparib significantly improved progression-free survival, with similar rates of response reported in patients with BRCA1- and BRCA2-mutated disease. Olaparib is generally well tolerated; the most commonly reported adverse events in clinical trials were mild nausea, fatigue, vomiting, and diarrhea. Severe anemia and severe fatigue can occur in association with olaparib treatment. Concurrent administration of olaparib and strong or moderate inducers or inhibitors of cytochrome P-450 isozyme 3A should be avoided, as use of those agents may alter plasma concentrations of olaparib.
  
  
  CONCLUSIONS
  Olaparib is a novel PARP inhibitor that is efficacious and well tolerated in patients with BRCA-mutated advanced ovarian cancers who have received three or more lines of prior treatment.
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Madison, WI.
authors.forename: Marklie
authors.initials: M
authors.lastname: Munroe
authors.affiliation: School of Pharmacy, University of Wisconsin-Madison, Madison, WIAnalytical Laboratory for Pharmacokinetics, Pharmacodynamics and Pharmacogenomics, University of Wisconsin Carbone Comprehensive Cancer Center, Madison, WI. jill.kolesar@wisc.edu.
authors.forename: Jill
authors.initials: J
authors.lastname: Kolesar
mesh_terms: D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D010793:Phthalazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010879:Piperazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D010793:Phthalazines; D010879:Piperazines; C531550:olaparib