ENHANCEMENT OF RADIATION RESPONSE OF PROSTATIC-CARCINOMA BY TAXOL - THERAPEUTIC POTENTIAL FOR LATE-STAGE MALIGNANCY

Radiation therapy for advanced prostate cancer has dose-limiting compl ications and often results in limited tumor control. A combination of radiation and taxol, a potential radiation sensitizer, may enhance the rapeutic efficacy at currently used individual doses. Human prostatic carcinoma lines in vitro, and Dunning rat prostatic adenocarcinoma in vivo, were treated with taxol and radiation individually, and in combi nation. Cytotoxicity of taxol was comparable between androgen sensitiv e and insensitive lines, with 50% growth inhibition at 9.6 to 12.7 nM. Combining agents increased cytotoxicity, with a dose modifying ratio of 1.8 at 0.1% survival. Flow cytometry showed an enhancement of radia tion toxicity associated with taxol-induced cell cycle phase arrest at G(2)/M. Injection of taxol (4 mg/kg/day x 5), radiation dose fraction ation (1.5 Gy/day x 5) and their combination significantly delayed Dun ning tumor growth. Adverse side effects were minimal The results imply that combination of these agents may have clinical potential in prost ate cancer treatment.