Pharmacogenetically driven patient selection for a first-in-human phase I trial of batracylin in patients with advanced solid tumors and lymphomas | Zendy

Shivaani Kummar | Zendy; Martin Gutierrez | Zendy; Lawrence W. Anderson | Zendy; Raymond W. Klecker | Zendy; Alice Chen | Zendy; Anthony J. Murgo | Zendy; James H. Doroshow | Zendy; Jerry M. Collins | Zendy

Open Access

Pharmacogenetically 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.

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