In vivo studies with the novel anticancer agent mitozolomide (NSC 353451) on Lewis lung carcinoma

Massimo Broggini, Eugenio Erba, Luciano Morasca, Carmel Horgan, Maurizio D'Incalci

Research output: Contribution to journalArticle

Abstract

Mitozolomide is one of the most effective drugs against Lewis lung carcinoma in the mouse. Two IP doses of 40 mg/kg (days 6 and 15 after IM transplantation of 3LL) or four doses of 20 mg/kg given at various intervals (starting from day 6) increased survival time by 100%. A single IP dose of 80 mg/kg was toxic, and 10 mg/kg was ineffective even when this dose was given on eight occasions. The pharmacokinetics of mitozolomide was investigated in 3LL-bearing mice by HPLC assay. Peak drug levels were achieved in tumor 15 min after IP treatment, after which they declined according to first-order kinetics, with a half-life of 80-100 min (the same as in plasma). No dose-dependent kinetics was observed. Flow cytometry studies showed an accumulation of 3LL cells in G2M 24 h after drug treatment. This cell cycle perturbation was reversed 96 h after the inactive dose of 10 mg/kg, but not after the effective dose of 40 mg/kg.

Original languageEnglish
Pages (from-to)125-128
Number of pages4
JournalCancer Chemotherapy and Pharmacology
Volume16
Issue number2
DOIs
Publication statusPublished - Mar 1986

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

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