keyword
MENU ▼
Read by QxMD icon Read
search

Veliparib

keyword
https://www.readbyqxmd.com/read/28723663/a-network-meta-analysis-on-the-efficacy-of-targeted-agents-in-combination-with-chemotherapy-for-treatment-of-advanced-metastatic-triple-negative-breast-cancer
#1
Long Ge, Yan Tang, Qiu-Ning Zhang, Jin-Hui Tian, Xiao-Hu Wang, Dawid Pieper, Bei Pan, Lun Li, Juan Ling, Zhi-Tong Bing, Ke-Hu Yang
OBJECTIVE: Our network meta-analysis aimed to determine the assistant efficacy of targeted therapy in combined with chemotherapy for advanced/metastatic triple-negative breast cancer (TNBC). RESULTS: A total of 15 randomized controlled trials (RCTs), involving 2,410 patients, met our inclusion criteria. Eight targeted agents involving 11 treatment arms were included. The methodological quality of included RCTs was acceptable. The results of direct comparisons showed that progression-free survival (PFS) was significantly longer with bevacizumab+chemotherapy when compared to chemotherapy alone (hazard ratio [HR] = 0...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28665051/a-phase-1-dose-escalation-study-of-single-agent-veliparib-in-japanese-patients-with-advanced-solid-tumors
#2
Tadaaki Nishikawa, Koji Matsumoto, Kenji Tamura, Hiroyuki Yoshida, Yuichi Imai, Aki Miyasaka, Takuma Onoe, Satoshi Yamaguchi, Chikako Shimizu, Kan Yonemori, Tatsunori Shimoi, Mayu Yunokawa, Hao Xiong, Silpa Nuthalapati, Hideyuki Hashiba, Tsukasa Kiriyama, Terri Leahy, Philip Komarnitsky, Keiichi Fujiwara
Veliparib (ABT-888) is a potent, orally bioavailable poly(ADP-ribose) polymerase-1 and -2 inhibitor. This phase 1 study evaluated the tolerability, pharmacokinetic profile, safety, and preliminary antitumor activity of single-agent veliparib in Japanese patients with advanced solid tumors. Eligible patients were assigned to treatment with veliparib at 200 mg or 400 mg dose; veliparib was self-administered orally twice daily on days 1-28 of 28-day cycles. Dose escalation, following a 3+3 design, defined dose-limiting toxicities, the maximum tolerated dose, and the recommended phase 2 dose...
June 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/28497757/safety-and-tolerability-of-veliparib-combined-with-capecitabine-plus-radiotherapy-in-patients-with-locally-advanced-rectal-cancer-a-phase-1b-study
#3
Brian G Czito, Dustin A Deming, Gayle S Jameson, Mary F Mulcahy, Houman Vaghefi, Matthew W Dudley, Kyle D Holen, Angela DeLuca, Rajendar K Mittapalli, Wijith Munasinghe, Lei He, John R Zalcberg, Samuel Y Ngan, Philip Komarnitsky, Michael Michael
BACKGROUND: Further optimisation of present standard chemoradiation is needed in patients with locally advanced rectal cancer. Veliparib, an oral poly(ADP-ribose) polymerase inhibitor, has been shown to enhance the antitumour activity of chemotherapy and radiotherapy in preclinical models. We aimed to establish the maximum tolerated dose and establish the recommended phase 2 dose of veliparib combined with neoadjuvant capecitabine and radiotherapy. METHODS: This phase 1b, open-label, multicentre, dose-escalation study was done at six hospitals (one in Australia and five in the USA)...
June 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28497258/clinical-pharmacokinetics-and-mass-balance-of-veliparib-in-combination-with-temozolomide-in-subjects-with-nonhematologic-malignancies
#4
Silpa Nuthalapati, Wijith Munasinghe, Vincent Giranda, Hao Xiong
BACKGROUND AND OBJECTIVES: Veliparib is an orally active potent poly(ADP-ribose) polymerase (PARP) inhibitor currently in phase III clinical trials in solid tumors. This phase I study evaluated the pharmacokinetics and mass balance of veliparib administered alone and in combination with temozolomide, and assessed any potential pharmacokinetic drug-drug interaction between veliparib and temozolomide. METHODS: This was an open-label, dose-escalation study of veliparib in combination with temozolomide in 42 subjects with nonhematologic malignancies...
May 11, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28461256/smoking-history-predicts-sensitivity-to-parp-inhibitor%C3%A2-veliparib-in-patients-with-advanced-non-small-cell-lung-cancer
#5
Martin Reck, Normand Blais, Erzsebet Juhasz, Vera Gorbunova, C Michael Jones, Laszlo Urban, Sergey Orlov, Fabrice Barlesi, Ebenezer Kio, Ulrich Keilholz, Qin Qin, Jiang Qian, Caroline Nickner, Juliann Dziubinski, Hao Xiong, Rajendar K Mittapalli, Martin Dunbar, Peter Ansell, Lei He, Mark McKee, Vincent Giranda, Suresh S Ramalingam
INTRODUCTION: Tobacco-related NSCLC is associated with reduced survival and greater genomic instability. Veliparib, a potent poly(adenosine diphosphate-ribose) polymerase inhibitor, augments platinum-induced DNA damage. A phase 2 trial of untreated advanced NSCLC showed a trend for improved outcomes (hazard ratio [HR] = 0.80, 95% confidence interval: 0.54-1.18, p = 0.27 for overall survival and HR = 0.72, 95% CI: 0.45-1.15, p = 0.17 for progression-free survival) when veliparib was added to carboplatin/paclitaxel...
July 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28387939/parent-metabolite-pharmacokinetic-modeling-and-pharmacodynamics-of-veliparib-abt-888-a-parp-inhibitor-in-patients-with-brca-1-2-mutated-cancer-or-parp-sensitive-tumor-types
#6
Jing Niu, Christie Scheuerell, Shailly Mehrotra, Sharon Karan, Shannon Puhalla, Brian F Kiesel, Jiuping Ji, Edward Chu, Mathangi Gopalakrishnan, Vijay Ivaturi, Jogarao Gobburu, Jan H Beumer
Veliparib (ABT-888) is a novel oral poly-ADP-ribose polymerase (PARP) inhibitor that is being developed for the treatment of hematologic malignancies and solid tumors. Although the pharmacokinetics of veliparib have been studied in combination with cytotoxic agents, limited information exists regarding the pharmacokinetics (PK) of chronically dosed single-agent veliparib in patients with either BRCA 1/2-mutated cancer or PARP-sensitive tumors. The objectives of the current analysis were to characterize the population pharmacokinetics of veliparib and its primary, active metabolite, M8, and to evaluate the relationship between veliparib and M8 concentrations and poly-ADP-ribose (PAR) level observed in peripheral blood mononuclear cells (PBMCs)...
August 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28356425/efficacy-of-the-parp-inhibitor-veliparib-with-carboplatin-or-as-a-single-agent-in-patients-with-germline-brca1-or-brca2-associated-metastatic-breast-cancer
#7
George Somlo, Paul Frankel, Banu Arun, Cynthia X Ma, Agustin Garcia, Tessa Cigler, Leah Cream, Harold Harvey, Joseph A Sparano, Rita Nanda, Helen K Chew, Timothy Moynihan, Matthew P Goetz, Linda Vahdat, Jan H Beumer, Arti Hurria, Joanne Mortimer, Richard Piekarz, Sharon Sand, Josef Herzog, Lily R Van Tongeren, Katherine Ferry-Galow, Alice Chen, Christopher Ruel, Edward Newman, David R Gandara, Jeffrey N Weitzel
We aimed to establish the maximum tolerated dose (MTD) of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2-(BRCA)-associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment post-progression, and to correlate PAR levels with clinical outcome. <br /><br />Experimental Design:Phase I patients received carboplatin (AUC of 5-6, every 21 days), with escalating doses of oral twice-daily (BID) veliparib...
March 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28314788/the-parp-inhibitor-veliparib-can-be-safely-added-to-bendamustine-and-rituximab-and-has-preliminary-evidence-of-activity-in-b-cell-lymphoma
#8
Jacob D Soumerai, Andrew D Zelenetz, Craig H Moskowitz, M Lia Palomba, Paul A Hamlin, Ariela Noy, David J Straus, Alison J Moskowitz, Anas Younes, Matthew J Matasar, Steven M Horwitz, Carol S Portlock, Jason A Konner, Mrinal M Gounder, David M Hyman, Martin H Voss, Matthew G Fury, Devika Gajria, Richard D Carvajal, Alan L Ho, Jan H Beumer, Brian Kiesel, Zhigang Zhang, Alice Chen, Richard F Little, Christine Jarjies, Thu O Dang, Fallon France, Nishant Mishra, John F Gerecitano
Purpose: The PARP inhibitor veliparib enhances the cytotoxicity of alkylating agents. This phase I study evaluated veliparib with the bifunctional alkylator bendamustine (VB) in patients with relapsed/refractory lymphoma, multiple myeloma, and solid malignancies, with a cohort expansion of VB with rituximab (VBR) in patients with B-cell lymphomas.Experimental Design: This dose-escalation study evaluated safety, pharmacokinetics, and preliminary efficacy of veliparib (20-400 mg twice a day, days 1-7 of 28-day cycle) and bendamustine (70 and 90 mg/m(2) intravenously, days 1 and 2)...
March 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28314386/veliparib-in-combination-with-radiotherapy-for-the-treatment-of-mgmt-unmethylated-glioblastoma
#9
Toni Rose Jue, Kyoko Nozue, Ashleigh J Lester, Swapna Joshi, Lisette B W Schroder, Shane P Whittaker, Sheri Nixdorf, Robert W Rapkins, Mustafa Khasraw, Kerrie L McDonald
BACKGROUND: The O (6) -methylguanine methyltransferase (MGMT) gene is frequently unmethylated in patients with glioblastoma (GBM), rendering them non-responsive to the standard treatment regime of surgery followed by concurrent radiotherapy (RT) and temozolomide. Here, we investigate the efficacy of adding a PARP inhibitor, veliparib, to radiotherapy to treat MGMT unmethylated GBM. METHODS: The inhibition of PARP with veliparib (ABT-888), a potent and orally bioavailable inhibitor in combination with RT was tested on a panel of patient derived cell lines (PDCLs) and patient-derived xenografts (PDX) models generated from GBM patients with MGMT unmethylated tumors...
March 17, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28243955/development-of-a-level-a-in-vitro-in-vivo-correlation-for-veliparib-abt-888-extended-release-tablet-formulation
#10
Rajendar K Mittapalli, Silpa Nuthalapati, Alyssa E Delke DeBord, Hao Xiong
PURPOSE: The aim of the current manuscript is to develop and validate a level A in vitro-in vivo correlation (IVIVC) for veliparib extended-release (ER) tablet formulations. METHODS: The in vitro release profiles of veliparib formulations were determined using USP Dissolution Apparatus 2 with 900 mL of 0.1 N HCl at 75 rpm. In a clinical study, 24 subjects with solid tumors received one of the ER formulations (200 mg): fast (Formulation A), intermediate (Formulation B), and slow (Formulation C), and two 100 mg immediate release capsules (Formulation D)...
June 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28156017/population-pharmacokinetics-and-site-of-action-exposures-of-veliparib-with-topotecan-plus-carboplatin-in-patients-with-haematological-malignancies
#11
Shailly Mehrotra, Mathangi Gopalakrishnan, Jogarao Gobburu, Jacqueline M Greer, Richard Piekarz, Judith E Karp, Keith Pratz, Michelle A Rudek
AIMS: Veliparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP) enzyme. The objectives of the analysis were to evaluate the effect of baseline covariates and co-administration of topotecan plus carboplatin (T + C) on pharmacokinetics of veliparib in patients with refractory acute leukaemia, and compare veliparib concentration in various biological matrices. METHODS: A population pharmacokinetic model was developed and effect of age, body size indices, sex, creatinine clearance (CrCL) and co-administration of T + C on the pharmacokinetics of veliparib were evaluated...
August 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28109627/a-final-report-of-a-phase-i-study-of-veliparib-abt-888-in-combination-with-low-dose-fractionated-whole-abdominal-radiation-therapy-ldfwar-in-patients-with-advanced-solid-malignancies-and-peritoneal-carcinomatosis-with-a-dose-escalation-in-ovarian-and-fallopian
#12
Kim A Reiss, Joseph M Herman, Deborah Armstrong, Marianna Zahurak, Anthony Fyles, Anthony Brade, Michael Milosevic, Laura A Dawson, Angela Scardina, Patricia Fischer, Amy Hacker-Prietz, Robert J Kinders, Lihua Wang, Alice Chen, Sarah Temkin, Naomi Horiba, Lee-Anne Stayner, Lillian L Siu, Nilofer S Azad
BACKGROUND: The combination of low-dose radiation therapy with PARP inhibition enhances anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with ABT-888 in patients with peritoneal carcinomatosis with a dose escalation in ovarian and fallopian cancer patients (OV). METHODS: Patients were treated with veliparib, 40-400mg orally BID on days 1-21 of 3 28-day cycles on 6 dose levels. Dose levels 5 and 6 included only OV patients...
March 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#13
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28031413/let-7-status-is-crucial-for-parp1-expression-in-her2-overexpressing-breast-tumors
#14
Monica E Wielgos, Rajani Rajbhandari, Tiffiny S Cooper, Shi Wei, Susan Nozell, Eddy S Yang
HER2(+) breast tumors have been shown to express elevated levels of PARP1 protein. Yet, the mechanism by which PARP1 is upregulated in HER2(+) breast cancer is unknown. Here, knockdown of HER2 (ERBB2) in HER2(+) breast cancer cells resulted in a reduction in PARP1 protein. Conversely, ectopic overexpression of HER2 in a non-HER2-overexpressing cell line resulted in increased PARP1 protein levels. Alterations in HER2 expression had no significant effect on PARP1 transcript levels. Instead, HER2 mRNA status was inversely correlated with let-7a miRNA levels in breast cancer cells...
March 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28001384/structural-basis-for-potency-and-promiscuity-in-poly-adp-ribose-polymerase-parp-and-tankyrase-inhibitors
#15
Ann-Gerd Thorsell, Torun Ekblad, Tobias Karlberg, Mirjam Löw, Ana Filipa Pinto, Lionel Trésaugues, Martin Moche, Michael S Cohen, Herwig Schüler
Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective...
February 23, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27998970/a-phase-i-trial-of-paclitaxel-cisplatin-and-veliparib-in-the-treatment-of-persistent-or-recurrent-carcinoma-of-the-cervix-an-nrg-oncology-study-nct-01281852
#16
P H Thaker, R Salani, W E Brady, H A Lankes, D E Cohn, D G Mutch, R S Mannel, K M Bell-McGuinn, P A Di Silvestro, D Jelovac, J S Carter, W Duan, K E Resnick, D S Dizon, C Aghajanian, P M Fracasso
Background: Preclinical studies demonstrate poly(ADP-ribose) polymerase (PARP) inhibition augments apoptotic response and sensitizes cervical cancer cells to the effects of cisplatin. Given the use of cisplatin and paclitaxel as first-line treatment for persistent or recurrent cervical cancer, we aimed to estimate the maximum tolerated dose (MTD) of the PARP inhibitor veliparib when added to chemotherapy. Patients and methods: Women with persistent or recurrent cervical carcinoma not amenable to curative therapy were enrolled...
March 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/27866910/proteome-wide-profiling-of-clinical-parp-inhibitors-reveals-compound-specific-secondary-targets
#17
Claire E Knezevic, Gabriela Wright, Lily L Remsing Rix, Woosuk Kim, Brent M Kuenzi, Yunting Luo, January M Watters, John M Koomen, Eric B Haura, Alvaro N Monteiro, Caius Radu, Harshani R Lawrence, Uwe Rix
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a promising class of targeted cancer drugs, but their individual target profiles beyond the PARP family, which could result in differential clinical use or toxicity, are unknown. Using an unbiased, mass spectrometry-based chemical proteomics approach, we generated a comparative proteome-wide target map of the four clinical PARPi, olaparib, veliparib, niraparib, and rucaparib. PARPi as a class displayed high target selectivity. However, in addition to the canonical targets PARP1, PARP2, and several of their binding partners, we also identified hexose-6-phosphate dehydrogenase (H6PD) and deoxycytidine kinase (DCK) as previously unrecognized targets of rucaparib and niraparib, respectively...
December 22, 2016: Cell Chemical Biology
https://www.readbyqxmd.com/read/27831000/targeted-therapies-for-the-treatment-of-non-small-cell-lung-cancer-monoclonal-antibodies-and-biological-inhibitors
#18
REVIEW
Ana P S Silva, Priscila V Coelho, Maristella Anazetti, Patricia U Simioni
The usual treatments for patients with non-small-cell lung cancer (NSCLC), such as advanced lung adenocarcinoma, are unspecific and aggressive, and include lung resection, radiotherapy and chemotherapy. Recently, treatment with monoclonal antibodies and biological inhibitors has emerged as an effective alternative, generating effective results with few side effects. In recent years, several clinical trials using monoclonal antibodies presented potential benefits to NSCLC, and 4 of them are already approved for the treatment of NSCLC, such as cetuximab, bevacizumab, nivolumab and pembrolizumab...
April 3, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27811964/the-poly-adp-ribose-polymerase-inhibitor-veliparib-and-radiation-cause-significant-cell-line-dependent-metabolic-changes-in-breast-cancer-cells
#19
Vijesh J Bhute, Yan Ma, Xiaoping Bao, Sean P Palecek
Breast tumors are characterized into subtypes based on their surface marker expression, which affects their prognosis and treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in clinical trials, both as single agents and in combination with other chemotherapeutics, in several subtypes of breast cancer patients. Here, we used NMR-based metabolomics to probe cell line-specific effects of the PARP inhibitor Veliparib and radiation on metabolism in three breast cancer cell lines...
November 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27803064/randomized-placebo-controlled-phase-ii-study-of-veliparib-in-combination-with-carboplatin-and-paclitaxel-for-advanced-metastatic-non-small-cell-lung-cancer
#20
RANDOMIZED CONTROLLED TRIAL
Suresh S Ramalingam, Normand Blais, Julien Mazieres, Martin Reck, C Michael Jones, Erzsebet Juhasz, Laszlo Urban, Sergey Orlov, Fabrice Barlesi, Ebenezer Kio, Ulrich Keiholz, Qin Qin, Jiang Qian, Caroline Nickner, Juliann Dziubinski, Hao Xiong, Peter Ansell, Mark McKee, Vincent Giranda, Vera Gorbunova
Purpose: PARP plays an important role in DNA repair. Veliparib, a PARP inhibitor, enhances the efficacy of platinum compounds and has been safely combined with carboplatin and paclitaxel. The primary endpoint of this phase II trial determined whether addition of veliparib to carboplatin and paclitaxel improved progression-free survival (PFS) in previously untreated patients with advanced/metastatic non-small cell lung cancer.Experimental Design: Patients were randomized 2:1 to carboplatin and paclitaxel with either veliparib or placebo...
April 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
keyword
keyword
18793
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"