TAXOL IN COMBINATION WITH ACUTE AND LOW-DOSE RATE IRRADIATION

Taxol is an investigational antineoplastic agent which acts by stabili zing microtubules, thereby preventing normal mitosis. It is believed t o block cells in the G(2)/M phase of the cell cycle. The drug is a nat ural product isolated from the yew, Taxus brevifolia. We have used a c ell line derived from human cervical carcinoma to investigate the comb ination of Taxol with high and low dose rate Cs-137 irradiation. An ad ditive effect for Taxol plus radiation was observed; supra-additivity or synergism is not suggested by our data. In the cell line studied, d rug concentrations that accumulate cells to some degree in the G(2)/M phase of the cycle lead to cell lethality, so that no radiosensitizing effect is possible. We have also shown that the cytotoxic effect of T axol is not limited to the G(2)/M phase of the cell cycle. In the clin ic, Taxol shows promise both as a chemotherapeutic agent and as a poss ible adjunct to radiation. The present work demonstrates the need for further studies of Taxol plus radiation with a variety of human cell l ines of normal and malignant origin.