A phase I and pharmacokinetic study of docetaxel combined with Doxil (pegylated liposomal doxorubicin) without and with granulocyte colony stimulating factor. Academic Article uri icon

Overview

abstract

  • The purpose of this study was (i) to determine the maximum tolerated dose (MTD) of docetaxel that can be administered in combination with Doxil, given without and with granulocyte colony stimulating factor (G-CSF), (ii) to define the pharmacokinetics (PK) of docetaxel when used in combination with Doxil, and (iii) to make preliminary observations on the anti-tumor activity of this combination in patients with metastatic solid tumors. Thirty-seven patients with metastatic cancer were enrolled. Courses were repeated every 3 weeks. Patients received a fixed dose of Doxil 30 mg/m(2) in combination with escalating doses of docetaxel ranging from 40 to 100 mg/m(2). After encountering dose-limiting febrile neutropenia, subsequent escalation was accomplished with G-CSF support. Selected patients at the recommended phase II dose underwent PK evaluation. The most common toxicity observed was neutropenia. Dose-limiting toxicity (30 mg/m(2) Doxil + 80 mg/m(2) docetaxel) was febrile neutropenia in three of six patients treated without G-CSF. Major non-hematological toxicities included alopecia, mucositis and hand-foot syndrome, and were observed after cumulative doses of chemotherapy. Objective responses (complete/partial) were documented in eight of 37 patients (four with breast cancer) and stable disease was seen in 17 patients. PK studies showed an increased tissue retention (decreased clearance) of docetaxel when given with Doxil. The recommended phase II dose of Doxil/docetaxel is 30/60 mg/m(2), q3 weeks, without G-CSF. Further dose escalation to 30/80 mg/m(2) is safe with G-CSF support. Anti-tumor activity, particularly against breast cancer, was observed at various dose levels. Our observations should provide evidence for phase II studies of this combination in patients with breast cancer and other anthracycline/taxane-sensitive cancers.

authors

  • Pavlick, Anna C
  • Chodkiewicz, Catherine
  • Liebes, Leonard
  • Hamilton, Anne
  • Wasserheit, Carolyn
  • Hochster, Howard
  • Speyer, James
  • Phillips, Zoë
  • Downey, Andrea
  • Sorich, Joan
  • Muggia, Franco

publication date

  • February 1, 2004

Research

keywords

  • Clinical Trials, Phase I as Topic
  • Doxorubicin
  • Granulocyte Colony-Stimulating Factor
  • Taxoids

Identity

Scopus Document Identifier

  • 12144289208

Digital Object Identifier (DOI)

  • 10.1097/00001813-200402000-00004

PubMed ID

  • 15075667

Additional Document Info

volume

  • 15

issue

  • 2