Phase I study of vintriptol, a tryptophan ester of vinblastine

Eur J Cancer. 1991;27(10):1222-6. doi: 10.1016/0277-5379(91)90085-r.

Abstract

Vintriptol, a tryptophan ester of vinblastine, is a new vinca alkaloid derivative. Preclinical studies have demonstrated its antitumour activity in a large variety of animal models. In this phase I study, 47 patients with advanced cancer were exposed to escalating doses of vintriptol, starting at 6 mg/m2 and following a modified Fibonacci schedule. The drug was administered as an intravenous push on a weekly schedule. Myelosuppression was the dose-limiting toxicity and the maximum tolerated dose was 45 mg/m2. Other toxicities consisted of mild nausea and vomiting and the occurrence of fever and dryness of the mouth immediately after drug administration. Neurotoxicity, a major side-effect of other vinca alkaloids, was insignificant. 1 partial remission in a patient suffering from colorectal cancer and 1 minor response in a patient with a metastatic tumour of the cutaneous appendagous glands were documented. Pharmacokinetics of vintriptol were evaluated at the highest dose levels. A dose schedule of 40 mg/m2 vintriptol per week is recommended for phase II studies.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Drug Evaluation
  • Female
  • Fever / chemically induced
  • Humans
  • Leukopenia / chemically induced
  • Male
  • Middle Aged
  • Neoplasms / blood
  • Neoplasms / drug therapy
  • Thrombocytopenia / chemically induced
  • Vinblastine / analogs & derivatives*
  • Vinblastine / therapeutic use

Substances

  • Antineoplastic Agents
  • vintriptol
  • Vinblastine