Open AccessPharmacogenetically driven patient selection for a first-in-human phase I trial of batracylin in patients with advanced solid tumors and lymphomas
Author(s) -
Shivaani Kummar,
Martin Gutierrez,
Lawrence W. Anderson,
Raymond W. Klecker,
Alice Chen,
Anthony J. Murgo,
James H. Doroshow,
Jerry M. Collins
Publication year - 2013
Publication title -
cancer chemotherapy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.112
H-Index - 111
eISSN - 1432-0843
pISSN - 0344-5704
DOI - 10.1007/s00280-013-2244-4
Subject(s) - medicine , pharmacokinetics , metabolite , toxicity , refractory (planetary science) , gastroenterology , pharmacology , maximum tolerated dose , biology , astrobiology
Batracylin (daniquidone), an ATP-insensitive topoisomerase I/II inhibitor, demonstrated wide interspecies variation in preclinical models consistent with formation of a toxic metabolite, N-acetyl-batracylin, following metabolism by N-acetyl-transferase 2 (NAT2). To minimize exposure to this toxic metabolite, this first-in-human study was conducted in patients with advanced refractory solid tumors or lymphomas demonstrated to have a slow NAT2 acetylator genotype. The objectives were to determine the safety, maximum tolerated dose (MTD), and pharmacokinetics of batracylin and its metabolites.