Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity.
Chlorozotocin is a glucose-substituted chloroethyl nitrosourea with pharmacologic properties suggesting it is a relatively nonmyelosuppressive cancer chemotherapy drug. Preclinical studies have shown that this drug possesses approximately twice the in vitro alkylating activity of the chloroethyl nitrosoureas BCNU and CCNU. In the L1210 leukemia system, chlorozotocin has curative activity at doses that result in minimal bone marrow toxicity. In vitro studies of human bond marrow stem cells have shown that chlorozotocin is relatively sparing of these cells compared to BCNU. Phase I and phase II trials in man have been performed that show that chlorozotocin's dose-limiting toxicity is thrombocytopenia at doses greater than 120 mg/m2. In the phase II trial, 16% of patients with colon cancer and 20% of patients with malignant melanoma evidenced objective regression of disease. Chlorozotocin is now undergoing phase II evaluation in combination chemotherapy trials in colon and stomach cancer.[1]References
- Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity. Macdonald, J.S., Hoth, D., Schein, P.S. Recent Results Cancer Res. (1980) [Pubmed]
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