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Estramustine Sensitizes Human Glioblastoma Cells to Irradiation¹

Yale University School of Medicine, Section of Neurosurgery, Haven, Connecticut 06510

Estramustine is an estradiol-based antimicrotubule agent that accumulates in malignant glioma cells, resulting in a concentration-dependent inhibition of proliferation. This agent has been shown to synchronize human glioma cells at G₂-M consistent with its known effects on the mitotic spindle and potentially could be used as a radiation enhancer. We determined the effects of estraumstine on the cell cycle of glioblastoma cells by flow cytometry. These findings were compared with clonogenic survival in cells pretreated with varying concentrations of estramustine prior to irradiation. These experiments indicated that 24 h treatment with 1 µM estraumstine had no effect on the percentage of G₂-M cells and did not enhance the cytotoxic effects of radiation while 10 µM estramustine increased the G₂-M fraction by 100% associated with a potentiation factor as high as 8.5 and a relative radiation sensitivity at 70% cytotoxicity of 5.2 compared with 15.4 for control cells. Estramustine can be administered p.o. on a daily schedule with minimal systemic toxicity. These data suggest that estramustine may be an effective radiation enhancer for glioblastoma.

¹ Supported by NCI R01 CA 54746-01 (J.P.), Yale Comprehensive Cancer Center Flow Cytometry Facility, U.S. Public Health Service Grant CA-16359 from NCI, and by the Doris and Jules Stein Foundation.

² To whom requests for reprints should be addressed, at Section of Neurosurgy, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06510.

Received 12/16/93. Accepted 2/ 4/94.