Investigational New Drugs

, Volume 31, Issue 3, pp 616–622

A phase I study of DHP107, a mucoadhesive lipid form of oral paclitaxel, in patients with advanced solid tumors: Crossover comparisons with intravenous paclitaxel

  • Yong Sang Hong
  • Kyu-pyo Kim
  • Hyeong-Seok Lim
  • Kyun-Seop Bae
  • Min-Hee Ryu
  • Jae-Lyun Lee
  • Heung Moon Chang
  • Yoon-Koo Kang
  • Hyeyoun Kim
  • Tae Won Kim
PHASE I STUDIES

DOI: 10.1007/s10637-012-9841-7

Cite this article as:
Hong, Y.S., Kim, K., Lim, HS. et al. Invest New Drugs (2013) 31: 616. doi:10.1007/s10637-012-9841-7

Summary

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/m2) during the first chemotherapy cycle, and intravenous paclitaxel 175 mg/m2 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/m2). Further dose escalation was not performed because pharmacokinetics did not increase proportionally at doses above 250 mg/m2. The coefficient of variance of AUClast DHP107 ranged from 11.8 % to 34.0 %, comparable to 24.4 % of intravenous paclitaxel 175 mg/m2. 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/m2 of DHP107, the dose escalation of DHP107 may be limited to 250 mg/m2 in further clinical trials.

Keywords

DHP107Oral paclitaxelPharmacokineticsPhase I

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Yong Sang Hong
    • 1
  • Kyu-pyo Kim
    • 1
  • Hyeong-Seok Lim
    • 2
  • Kyun-Seop Bae
    • 2
  • Min-Hee Ryu
    • 1
  • Jae-Lyun Lee
    • 1
  • Heung Moon Chang
    • 1
  • Yoon-Koo Kang
    • 1
  • Hyeyoun Kim
    • 3
  • Tae Won Kim
    • 1
  1. 1.Department of OncologyAsan Medical Center, University of Ulsan College of MedicineSongpa-guSouth Korea
  2. 2.Department of Clinical Pharmacology and TherapeuticsAsan Medical Center, University of Ulsan College of MedicineSeoulSouth Korea
  3. 3.Product Planning & Development DepartmentDAE HWA Pharmaceutical Co., Ltd.HoengseongSouth Korea