biostudies-literatureTan ARUPCI Cancer Pharmacokinetics and Pharmacodynamics FacilityNational Cancer InstituteNCI NIH HHS49-58https://www.ebi.ac.uk/biostudies/studies/S-EPMC8934569biostudies-literatureUnknown89(1)<h4>Purpose</h4>Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C.<h4>Methods</h4>Objectives were to establish the maximum tolerated dose (MTD) of the combinations, characterize V pharmacokinetics (PK) in the presence and absence of C, measure PAR in peripheral blood mononuclear cells (PBMCs) and γH2AX in circulating tumor cells (CTCs). In Group 1, dose escalations of V from 10 to 50 mg every 12 h Days 1-4 plus C 450 to 750 mg/m² Day 3 in 21-day cycles were evaluated. In Group 2, V doses ranged from 50 to 150 mg every 12 h Days 1-4 with AC (60/600 mg/m²) Cancer chemotherapy and pharmacologyA phase I study of veliparib with cyclophosphamide and veliparib combined with doxorubicin and cyclophosphamide in advanced malignancies.PMC8934569UM1-CA-186690R50CA211241UM1 CA186716U01-CA099168U01 CA132194U24 CA247643U01 CA099168UM1-CA-186716P30 CA047904UM1 CA186690U01-CA-132194-01P30-CA47904R50 CA211241Shah MGounder MMalhotra JKane MPMehnert JMKiesel BFLin YJi JBeumer JHAisner JTan ARStein MNChen ALin HChan NMoss RAfalseA phase I study of veliparib with cyclophosphamide and veliparib combined with doxorubicin and cyclophosphamide in advanced malignancies.<h4>Purpose</h4>Veliparib (V), an oral poly(ADP-ribose) polymerase (PARP) inhibitor, potentiates effects of alkylating agents and topoisomerase inhibitors in preclinical tumor models. We conducted a phase I trial of V with iv cyclophosphamide (C) and V plus iv doxorubicin (A) and C.<h4>Methods</h4>Objectives were to establish the maximum tolerated dose (MTD) of the combinations, characterize V pharmacokinetics (PK) in the presence and absence of C, measure PAR in peripheral blood mononuclear cells (PBMCs) and γH2AX in circulating tumor cells (CTCs). In Group 1, dose escalations of V from 10 to 50 mg every 12 h Days 1-4 plus C 450 to 750 mg/m² Day 3 in 21-day cycles were evaluated. In Group 2, V doses ranged from 50 to 150 mg every 12 h Days 1-4 with AC (60/600 mg/m²) 2022-01-01T00:00:00Z2022 Jan2025-04-19T18:08:13.337Z2025-04-19T18:08:13.337ZS-EPMC89345693466902310.1007/s00280-021-04350-x