A Phase I and Pharmacokinetic Study of CBT-1 as a Multidrug Resistance Modulator in the Treatment of Patients with Advanced Cancer

Abstract

CBT-1, a natural product, was studied in an escalating dose Phase I clinical trial with doxorubicin at 60 mg/m². CBT-1 was administered by mouth at doses from 200 mg/m² to 600 mg/m². The drug was given for 7 days and doxorubicin administered intravenously on day 6. The MTD was determined to be 500 mg/m² although some patients did tolerate 600 mg/m² with moderate nausea and occasional vomiting. Side effects were otherwise mild in the 23 patients treated. Pharmacokinetic determinations in an additional 11 patients demonstrated that CBT-1 did not significantly alter the pharmacokinetics of doxorubicin. In this Phase I study, 25 of 34 patients were evaluable for response and 5 patients demonstrated tumor shrinkage.