Phase I trial of phenoxodiol delivered by continuous intravenous infusion in patients with solid cancer

Annals of Oncology : Official Journal of the European Society for Medical Oncology
Toni K ChoueiriR M Bukowski

Abstract

Phenoxodiol is a multi-pathway initiator of apoptosis with broad anti-tumor activity and high specificity for tumor cells. Its biochemical effects are particularly suited to reversal of chemo-resistance, and the drug is being developed as a chemo-sensitizer of standard chemotherapeutics in solid cancers. This phase I, single-center trial was conducted to test a continuous intravenous dosing regimen of phenoxodiol in patients with late-stage, solid tumors to determine toxicity, pharmacokinetics, and preliminary efficacy. Phenoxodiol given by intravenous infusion continuously for 7 days on 14-day cycles was dose-escalated on an inter-patient basis at dosages of 0.65,1.3, 3.3, 20.0, and 27.0 mg/kg/day (three to four patients per stratum). Treatment cycles continued until disease progression. Toxicity was based on standard criteria; efficacy was based on changes in tumor burden (WHO); pharmacokinetic analysis was conducted on plasma samples at specified time points during treatment cycles. Nineteen heavily-pre-treated patients with solid tumors received a median of three cycles of treatment (range 1-13); two patients received >or= 12 cycles. No dose-limiting toxicities were encountered, with emesis and fatigue (one patient) and ras...Continue Reading

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