TAXOL IN COMBINATION WITH ACUTE AND LOW-DOSE RATE IRRADIATION

Taxol is an investigational antineoplastic agent which acts by stabilizing microtubules, thereby preventing normal mitosis. It is believed to block cells in the G(2)/M phase of the cell cycle. The drug is a natural product isolated from the yew, Taxus brevifolia. We have used a cell line derived from human cervical carcinoma to investigate the combination of Taxol with high and low dose rate Cs-137 irradiation. An additive effect for Taxol plus radiation was observed; supra-additivity or synergism is not suggested by our data. In the cell line studied, drug 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 Taxol is not limited to the G(2)/M phase of the cell cycle. In the clinic, Taxol shows promise both as a chemotherapeutic agent and as a possible adjunct to radiation. The present work demonstrates the need for further studies of Taxol plus radiation with a variety of human cell lines of normal and malignant origin.