Invest New Drugs. 2013 Jun;31(3):616-22. doi: 10.1007/s10637-012-9841-7. Epub 2012 Jun 14.

A phase I study of DHP107, a mucoadhesive lipid form of oralpaclitaxel, in patients  with advanced solid tumors: crossovercomparisons with intravenous paclitaxel.

Hong YS, Kim KP, Lim HS, Bae KS, Ryu MH, Lee JL, Chang HM, Kang YK, Kim H, Kim TW.

Abstract

PURPOSE:

This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor.

PATIENTS AND METHODS: Patients with advanced solid tumors refractory to all standard treatments were administered a single oral dose of DHP107 on a dose-escalating schedule (60-600 mg/m(2)) during the first chemotherapy cycle, and intravenous paclitaxel 175 mg/m(2) during subsequent cycles. Cohorts of 3 patients were treated at each dose level provided no DLTs were observed. The pharmacokinetics of paclitaxel and its metabolites were investigated for oral DHP107 and intravenous paclitaxel.

RESULTS: Thirty-four patients were enrolled. Dose-limiting toxicities were not observed, even at the highest dose level (600 mg/m(2)). Further dose escalation was not performed because pharmacokinetics did not increase proportionally at doses above 250 mg/m(2). The coefficient of variance of AUClast DHP107 ranged from 11.8 % to 34.0 %, comparable to 24.4 % of intravenous paclitaxel 175 mg/m(2). There were no grade 4 toxicities, whereas grade 3 toxicities included diarrhea (12.1 %), neutropenia (6.1 %) and fatigue (3.0 %). While no objective responses were observed, 11 patients (33.3 %) showed stable disease.

CONCLUSIONS: DHP107 was safe and feasible in patients with advanced malignancies. As exposure of paclitaxel plateau among patients receiving more than 250 mg/m(2) of DHP107, the dose escalation of DHP107 may be limited to 250 mg/m(2) in further clinical trials.

PMID:

22695940

DOI:

10.1007/s10637-012-9841-7