Frequent administration of Dabis Maleate, a phase I study

Ann Oncol. 1992 Mar;3(3):241-2. doi: 10.1093/oxfordjournals.annonc.a058161.

Abstract

Dabis Maleate (1,4-bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1] Heptane dihydrogen dimaleate) (NSC 262666) is an alkylating quaternary nitrogen compound. In a previous phase I study using a once-every-3-weeks administration the dose-limiting toxicity was neurotoxicity and the recommended dose for phase II studies was 750 mg/m2 iv every 3 weeks. In vitro studies suggested a higher activity after more frequent administration, and in vivo studies a better therapeutic index with prolonged infusion. We studied 11 patients with solid tumors. Dose levels tested ranged from 250-750 mg/m2, either as a day 1-3 regimen or weekly, the latter as bolus administration or as prolonged infusion. The dose-limiting toxicity was neurotoxicity consisting of paresthesias and ataxia. Nausea and vomiting were moderate. No other major toxicity was observed. The dose recommended for phase II studies is 500 mg/m2/week as a 6-hour iv infusion for 6 weeks, followed by a 3-week rest period.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Bridged Bicyclo Compounds / administration & dosage*
  • Bridged Bicyclo Compounds, Heterocyclic*
  • Drug Administration Schedule
  • Drug Evaluation
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Quaternary Ammonium Compounds / administration & dosage*

Substances

  • Bridged Bicyclo Compounds
  • Bridged Bicyclo Compounds, Heterocyclic
  • Quaternary Ammonium Compounds
  • NSC 262266