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Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors.
Ruth Plummer
1 ,
Christopher Jones ,
Mark Middleton ,
Richard Wilson ,
Jeffrey Evans ,
Anna Olsen ,
Nicola Curtin ,
Alan Boddy ,
Peter McHugh ,
David Newell ,
Adrian Harris ,
Patrick Johnson ,
Heidi Steinfeldt ,
Raz Dewji ,
Diane Wang ,
Lesley Robson ,
Hilary Calvert
Dec 01 2008
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Abstract
One mechanism of tumor resistance to cytotoxic therapy is repair of damaged DNA. Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme involved in base excision repair, one of the five major repair pathways. PARP inhibitors are emerging as a new class of agents that can potentiate chemotherapy and radiotherapy. The article reports safety, efficacy, pharmacokinetic, and pharmacodynamic results of the first-in-class trial of a PARP inhibitor, AG014699, combined with temozolomide in adults with advanced malignancy.