The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial

• Published in: The lancet oncology Vol. 14; no. 9; pp. 882 - 892
• Main Authors: Sandhu, Shahneen K, Schelman, William R, Wilding, George, Moreno, Victor, Baird, Richard D, Miranda, Susana, Hylands, Lucy, Riisnaes, Ruth, Forster, Martin, Omlin, Aurelius, Kreischer, Nathan, Thway, Khin, Gevensleben, Heidrun, Sun, Linda, Loughney, John, Chatterjee, Manash, Toniatti, Carlo, Carpenter, Christopher L, Iannone, Robert, Kaye, Stan B, de Bono, Johann S, Wenham, Robert M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2013; Elsevier Limited
• Subjects: Adult; Aged; BRCA1 Protein - genetics; BRCA2 Protein - genetics; Cohort Studies; DNA repair; Drug dosages; Ewings sarcoma; Female; Follow-Up Studies; Genes; Hematology; Hematology, Oncology, and Palliative Medicine; Heterozygote; Humans; Indazoles - pharmacokinetics; Indazoles - therapeutic use; Male; Maximum Tolerated Dose; Middle Aged; Mutation; Mutation - genetics; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - genetics; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - pathology; Neutropenia; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Patients; Piperidines - pharmacokinetics; Piperidines - therapeutic use; Poly(ADP-ribose) Polymerase Inhibitors; Prognosis; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Tissue Distribution; Toxicity; Tumors; United States > US

Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tole...