Match!

Phase 1 study of the PARP inhibitor E7449 as a single agent in patients with advanced solid tumors or B-cell lymphoma.

Published on May 20, 2014in Journal of Clinical Oncology28.349
· DOI :10.1200/jco.2014.32.15_suppl.e19531
Ruth Plummer32
Estimated H-index: 32
(Freeman Hospital),
Divyanshu Dua2
Estimated H-index: 2
(St Thomas' Hospital)
+ 11 AuthorsDebashis Sarker20
Estimated H-index: 20
(Guy's and St Thomas' NHS Foundation Trust)
Abstract
e19531^ Background: E7449 is an orally bioavailable, likely brain penetrable, potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1 and PARP 2 with an IC50 of 1.0 and 1.2 nmol/L respectively. E7449 is a poor P-gp substrate. Preclinically, E7449 potentiates the antitumor activity of chemotherapy and radiotherapy and has activity as a single-agent in BRCA-deficient and other tumors. A Phase 1 study of E7449 as a single agent is underway to determine the MTD, safety, PK, PD, preliminary activity and perform exploratory biomarker analysis. Methods: Patients (pts) with advanced solid tumors or B-cell lymphoma, ECOG PS 0-1, > 18 years (yrs) and adequate organ function are eligible. E7449 is administered orally, once daily (QD), continuously. Blood samples for PK, PD and biomarkers are collected at multiple time points. Results: 25 pts (median age: 66 yrs; M/F: 14/ 11) have been treated at 6 dose levels: 50, 100, 200, 400, 800 and 600 mg QD. Tumor types included: pancreatic (n=5), lung (n=4), ...
  • References (0)
  • Citations (1)
📖 Papers frequently viewed together
19 Citations
8 Citations
6 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References0
Newest
Cited By1
Newest
#1Csaba Hegedűs (University of Debrecen)H-Index: 14
#2Gábor BorosH-Index: 4
Last. Éva RemenyikH-Index: 19
view all 12 authors...
Keratinocytes provide the first line of defense of the human body against carcinogenic ultraviolet (UV) radiation. Acute and chronic UVB-mediated cellular responses were widely studied. However, little is known about the role of mitochondrial regulation in UVB-induced DNA damage. Here, we show that poly (ADP-ribose) polymerase 1 (PARP1) and ataxia-telangiectasia-mutated (ATM) kinase, two tumor suppressors, are important regulators in mitochondrial alterations induced by UVB. Our study demonstrat...
2 CitationsSource
#1Sreejit Parameswaran (U of S: University of Saskatchewan)H-Index: 6
#2Deeksha Kundapur (U of S: University of Saskatchewan)H-Index: 1
Last. Franco J. Vizeacoumar (U of S: University of Saskatchewan)H-Index: 21
view all 6 authors...
Targeted therapies rely on the genetic and epigenetic status of the tumor cells and are seen as the most promising approach to treat cancer today. However, current targeted therapies focus on directly inhibiting those molecules that are altered in tumor cells. Unfortunately, targeting these molecules, even with specific inhibitors, is challenging as tumor cells rewire their genetic circuitry to eliminate genetic dependency on these targets. Here, we describe how synthetic lethality approaches ca...
4 CitationsSource