Phase I study of docetaxel plus ifosfamide in patients with advanced cancer

Br J Cancer. 2002 Oct 7;87(8):846-9. doi: 10.1038/sj.bjc.6600542.

Abstract

The aim of this study was to determine the maximum tolerated dose of a fixed dose of docetaxel when combined with continuous infusion ifosfamide, with and without G-CSF support, in the treatment of advanced cancer, and to evaluate anti-tumour activity of this combination. Thirty-one patients with advanced malignancies were treated with docetaxel 75 mg/m(2) intravenously on days 1, and ifosfamide at increasing dose levels from 1500 mg/m(2)/day to 2750 mg/m(2)/day as a continuous infusion from day 1-3, every 3 weeks. A total of 107 cycles of treatment were administered. Without G-CSF support dose-limiting toxicity of grade 4 neutropenia greater than 5 days duration occurred at dose level 1. With the addition of G-CSF the maximum tolerated dose was docetaxel 75 mg/m(2) on day 1 and ifosfamide 2750 mg/m(2)/day on days 1-3. Dose limiting toxicity (DLT) included ifosfamide-induced encephalopathy, febrile neutropenia and grade three mucositis. Three complete responses and 3 partial responses were seen. This combination of docetaxel and infusional ifosfamide is feasible and effective. The recommended dose for future phase II studies is docetaxel 75 mg/m(2) on day 1 and ifosfamide 2500 mg/m(2)/day continuous infusion on days 1-3.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Female
  • Gastrointestinal Diseases / chemically induced
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Hematologic Diseases / chemically induced
  • Humans
  • Ifosfamide / administration & dosage
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Paclitaxel / administration & dosage
  • Paclitaxel / analogs & derivatives*
  • Taxoids*

Substances

  • Taxoids
  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • Paclitaxel
  • Ifosfamide