Lomeguatrib, a Potent Inhibitor of O super(6)-Alkylguanine-DNA-Alkyltransferase: Phase I Safety, Pharmacodynamic, and Pharmacokinetic Trial and Evaluation in Combination with Temozolomide in Patients with Advanced Solid Tumors

• Published in: Clinical cancer research Vol. 12; no. 5; pp. 1577 - 1584
• Main Authors: Ranson, Malcolm, Middleton, Mark R, Bridgewater, John, Lee, Siow Ming, Dawson, Martin, Jowle, Debra, Halbert, Gavin, Waller, Sue, McGrath, Helen, Gumbrell, Lindsey, McElhinney, RStanley, Donnelly, Dorothy, McMurry, TBrian H, Margison, Geoffrey P
• Format: Journal Article
• Language: English
• Published: 01.03.2006

PURPOSE: A major mechanism of resistance to temozolomide involves the DNA repair protein O super(6)-alkylguanine-DNA-alkyltransferase (ATase). The main aims of this phase I trial were to determine an ATase-depleting dose (ADD) of lomeguatrib, a potent pseudosubstrate inhibitor, and to define a suita...