A Cancer Research UK phase I trial combining the dinitrobenzamide prodrug CB1954 (tretazicar) and the NQO2 substrate EP-0152R (caricotamide) intravenously (IV) every 3 weeks


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Emma Cattell1, Debashis Sarker3, Diana Anderson3, Victoria Spanswick4, Scott Davies2, R Agarwal3, Nicki Heywood1, David Kerr2, Ian Judson3, John Hartley4, Mark Middleton1

1Churchill Hospital, Oxford, UK, 2University of Oxford, UK,3Royal Marsden Hospital, Sutton, UK, 4University College London, UK

Abstract

Background

CB1954 (CB) is a dinitrobenzamide prodrug that is converted in the presence of the enzyme NQO2 and co-substrate EP-0152R (EP) into a potent cytotoxic bifunctional alkylating agent.

Method

Patients (pts) with histologically confirmed advanced solid tumours and WHO Performance Status 0 - 2 were treated with CB and EP. CB was administered IV over 15 minutes midway through a 4 hour IV infusion of EP every 3 weeks. Objectives were to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of the combination, evaluate pharmacokinetics (PK) and pharmacodynamic (PD) effects and describe antitumour activity.