Summary
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.
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Broggini, M., Erba, E., Morasca, L. et al. In vivo studies with the novel anticancer agent mitozolomide (NSC 353451) on Lewis lung carcinoma. Cancer Chemother. Pharmacol. 16, 125–128 (1986). https://doi.org/10.1007/BF00256161
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DOI: https://doi.org/10.1007/BF00256161