Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888; V) in combination with irinotecan (CPT-11; Ir) in patients (pts) with advanced solid tumors
| Autor: | Lance K. Heilbrun, Edward A. Sausville, Alice P. Chen, Jiuping Ji, Scott A. Boerner, Patricia LoRusso, Jing Li, M. J. Pilat, Geoffrey I. Shapiro, N. Nechiporchik, Daryn Smith, Ralph E. Parchment, Jingsong Zhang |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 29:3000-3000 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2011.29.15_suppl.3000 |
| Popis: | 3000 Background: The nuclear enzyme PARP is essential in recognition and repair of DNA damage. In preclinical models, PARP inhibitors work as sensitizing agents for DNA-damaging agents such as Ir. V is an orally bioavailable PARP 1 and 2 inhibitor. This phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), PK and PD of V together with Ir. Methods: Eligibility included patients with performance status 0-2; ≥ age 18; adequate bone marrow, hepatic and renal function. Cycles were 21 days. Ir was given i.v. 100 mg/m2 over 90 min on Days 1 and 8. Twice daily (BID) oral dosing of V (10-50mg) occurred Days 3-14 (Cycle 1) and Days -1-14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Tumor biopsies and matched peripheral blood mononuclear cells (PBMCs) were collected for PD evaluation of PAR, γ-H2AX, PARP1, TOPO1, and ERCC1 after Ir alone and after the combination. Results: 32 pts were treated (2 lung, 14 breas... |
| Databáze: | OpenAIRE |
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