A phase I clinical evaluation of 1-(2-chloroethyl)-3-[2-(dimethylaminosulphonyl)ethyl]-1-nitrosou rea (TCNU).
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.
Vibe-Petersen
J
J
Department of Oncology, Finsen Institute, Copenhagen, Denmark.
Bork
E
E
Møller
H
H
Hansen
H H
HH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009607:Nitrosourea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000091402:Prohibitins; D013654:Taurine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds; C000717331:PHB2 protein, human; D000091402:Prohibitins; D013654:Taurine; C052991:1-(2-chloroethyl)-3-(2-(dimethylaminosulfonyl)ethyl)-1-nitrosourea