Information about Talazoparib
Talazoparib is an orally available small molecule inhibitor of the DNA repair enzyme poly ADP-ribose polymerase (PARP) which is used as an antineoplastic agent in the treatment of selected cases of breast cancer.
Liver safety of Talazoparib
Talazoparib is associated with a moderate rate of serum aminotransferase elevations during therapy and is suspected to cause rare instances of clinically apparent acute liver injury.
Mechanism of action of Talazoparib
Talazoparib (tal" a zoe' pa rib) is a potent small molecule inhibitor of polyadenosine 5’-diphosphoribose (ADP-ribose) polymerase (PARP), an enzyme involved in repair of single strand breaks in DNA and which is used in the therapy of breast cancer. In normal cells, DNA repair mechanisms include base excision repair for single strand DNA breaks, for which PARP plays an important role, and homologous recombination for double-strand DNA breaks for which the tumor suppressor proteins BRCA-1 and BRCA-2 are involved. In patients with cancers associated with BRCA mutations, and particularly those with breast and ovarian cancer, the cancer cells are particularly susceptible to PARP inhibitors which cause accumulation of DNA breaks and resultant cell necrosis.
Clinical use of Talazoparib
In several clinical trials, talazoparib has been found improve progression free survival in patients with advanced or metastatic HER-2 negative breast cancer with BRCA mutations. It is also being evaluated as therapy of other types of solid tumors that harbor germ-line BRCA mutations.
FDA approval information for Talazoparib
Talazoparib was approved for therapy of breast cancer (HER negative, BRCA positive) in the United States in 2018 and is available in capsules of 0.25 and 1.0 mg under the brand name Talzenna.
Dosage and administration for Talazoparib
The recommended dose is 1 mg orally once daily, continued until progressive disease or intolerable toxicity occurs.
Side effects of Talazoparib
Side effects are common and can include fatigue, nausea, vomiting, diarrhea, anorexia, headache, alopecia, anemia, neutropenia and thrombocytopenia. Uncommon, but potentially severe side effects include myelodysplastic syndromes, marked myelosuppression and embryo-fetal toxicity.