A phase I clinical evaluation of 1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]-1-nitrosou rea (TCNU)

Eur J Cancer Clin Oncol. 1987 Dec;23(12):1837-43. doi: 10.1016/0277-5379(87)90049-6.

Abstract

TCNU (1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]-1-nitrosour ea) is a newly developed water-soluble nitrosourea based on the endogenous aminoethanesulphonic acid taurine. TCNU was in an extended phase I trial given orally every 4-8 weeks using a stepwise dose escalation from 20 to 170 mg/m2. One hundred and thirty-nine patients received a total of 323 courses. Minor haematologic toxicity was observed in 12 patients treated at dose levels less than 70 mg/m2. Thrombocytopenia WHO grades 1-4 occurred in 43% (55/127) and leucopenia WHO grades 1-3 in 45% (57/127) of the patients treated at dose levels greater than or equal to 70 mg/m2. Nausea and vomiting was recorded in about half the patients despite the use of metoclopramide. At the initial dose level 41 patients received greater than or equal to 3 courses of TCNU. Cumulative leucopenia and thrombocytopenia occurred in 3/41 and in 12/41 patients, respectively, while reversible hepatotoxicity was observed in two patients. Antitumour activity was observed in patients with advanced squamous cell, adeno- and large cell carcinoma of the lung. The recommended starting doses for phase II trials with TCNU are as follows: heavily pretreated patients 90 mg/m2, minimally/-moderately pretreated patients 110 mg/m2 and previously untreated patients 130 mg/m2 with TCNU given every 4-5 weeks, the repeated doses and intervals being adjusted to individual tolerance.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Dose-Response Relationship, Drug
  • Drug Evaluation
  • Hematologic Diseases / chemically induced
  • Humans
  • Middle Aged
  • Neoplasms / drug therapy*
  • Nitrosourea Compounds / adverse effects
  • Nitrosourea Compounds / therapeutic use*
  • Prohibitins
  • Taurine / adverse effects
  • Taurine / analogs & derivatives*
  • Taurine / therapeutic use

Substances

  • Antineoplastic Agents
  • Nitrosourea Compounds
  • PHB2 protein, human
  • Prohibitins
  • Taurine
  • 1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea