ABT-888 - CAS 912445-05-7
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Not Intended for Therapeutic Use. For research use only.
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1.Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer.
Rodler ET1, Kurland BF2, Griffin M3, Gralow JR3, Porter P3, Yeh RF3, Gadi VK3, Guenthoer J3, Beumer JH2, Korde L3, Strychor S2, Kiesel BF2, Linden HM3, Thompson JA3, Swisher E3, Chai X3, Shepherd S4, Giranda V4, Specht JM3. Clin Cancer Res. 2016 Jan 22. [Epub ahead of print]
PURPOSE: Cisplatin is synergistic with vinorelbine and the PARP inhibitor veliparib, and has antineoplastic activity in triple-negative breast cancer (TNBC) andBRCAmutation-associated breast cancer. This phase I study assessed veliparib with cisplatin and vinorelbine.
2.Randomized phase II trial of cyclophosphamide and the oral poly (ADP-ribose) polymerase inhibitor veliparib in patients with recurrent, advanced triple-negative breast cancer.
Kummar S1, Wade JL2, Oza AM3, Sullivan D4, Chen AP1, Gandara DR5, Ji J6, Kinders RJ6, Wang L6, Allen D1, Coyne GO1, Steinberg SM1, Doroshow JH7. Invest New Drugs. 2016 Mar 21. [Epub ahead of print]
Background In tumors carrying BRCA mutations, DNA damage caused by standard cytotoxic chemotherapy can be potentiated by poly [ADP-ribose] polymerase (PARP) inhibitors, leading to increased cell death through synthetic lethality. Individuals carrying mutations in BRCA have an increased incidence of triple negative breast cancer (TNBC). In order to assess the role of PARP inhibition in the treatment of TNBC, we conducted a randomized phase II trial of the combination of veliparib, a small molecule PARP inhibitor, with the cytotoxic agent cyclophosphamide versus cyclophosphamide alone in patients with refractory TNBC. Methods Adult patients with TNBC were randomized to receive oral cyclophosphamide 50 mg once daily with or without oral veliparib at 60 mg daily in 21-day cycles. Patients on the cyclophosphamide arm could crossover to the combination arm at disease progression. Results Forty-five patients were enrolled; 18 received cyclophosphamide alone and 21 received the combination as their initial treatment regimen.
3.Veliparib for the treatment of ovarian cancer.
Bogliolo S1, Cassani C1, Dominoni M1, Musacchi V1, Venturini PL2, Spinillo A1, Ferrero S2, Gardella B1. Expert Opin Investig Drugs. 2016 Mar;25(3):367-74. doi: 10.1517/13543784.2016.1146677. Epub 2016 Feb 16.
INTRODUCTION: Ovarian cancer represents the sixth most commonly diagnosed cancer among women, with an incidence of 6.1 cases per 100.000 women and a cumulative lifetime risk of 0.5%. Treatment is based on debulking surgery and platinum-based chemotherapy, with the potential combination with taxane. However, the recently available data on the genetic basis and aetiology of ovarian cancer has led to the development of new anticancer drugs. Poly(ADP-ribose) polymerase (PARP) inhibitors are one of the most promising new classes of targeted agents currently under investigation for the treatment of ovarian cancer. Veliparib is a small molecule that inhibits both PARP-1 and PARP-2 and was originally shown to be efficacious in BRCA-associated tumors.
4.Phase I safety, pharmacokinetic and pharmacodynamic study of the poly (ADP-ribose) polymerase inhibitor veliparib with irinotecan in patients with advanced solid tumors.
LoRusso PM1, Li J2, Burger A3, Heilbrun LK4, Sausville E5, Boerner S6, Smith D7, Pilat MJ8, Zhang J9, Tolaney S10, Cleary JM11, Chen A12, Rubinstein L13, Boerner JL14, Bowditch A9, Cai D15, Bell T15, Wolanski A15, Marrero A16, Zhang Y17, Ji JJ18, Ferry-Ga Clin Cancer Res. 2016 Feb 3. pii: clincanres.0652.2015. [Epub ahead of print]
BACKGROUND: Poly (ADP-ribose) polymerase (PARP) is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitormediated DNA damage. This Phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK) and pharmacodynamics (PD) of veliparib, an orally-bioavailable PARP 1/2 inhibitor, in combination with irinotecan.
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