Enhancement of radiation response of prostatic carcinoma by taxol: therapeutic potential for late-stage malignancy.
Radiation therapy for advanced prostate cancer has dose-limiting complications and often results in limited tumor control. A combination of radiation and taxol, a potential radiation sensitizer, may enhance therapeutic 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 combination. Cytotoxicity of taxol was comparable between androgen sensitive 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 radiation toxicity associated with taxol-induced cell cycle phase arrest at G2/M. Injection of taxol (4 mg/kg/day x 5), radiation dose fractionation (1.5 Gy/day x 5) and their combination significantly delayed Dunning tumor growth. Adverse side effects were minimal. The results imply that combination of these agents may have clinical potential in prostate cancer treatment.
Lokeshwar
B L
BL
Department of Urology, University of Miami School of Medicine, Florida 33101, USA.
Ferrell
S M
SM
Block
N L
NL
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use* / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D017239:Paclitaxel