Taxol: a novel radiation sensitizer.
The investigational antineoplastic agent, taxol, a natural product from the yew, Taxus sp. L., is currently being evaluated in a series of Phase II clinical trials. To date, the drug has shown activity against ovarian cancer, lung cancer, and melanoma. Taxol is a potent microtubule stabilizing agent that selectively blocks cells in the G2 and M phases of the cell cycle and is cytotoxic in a time-concentration dependent manner. It is well known from radiobiological principles that G2 and M are the most radiosensitive phases of the cell cycle. On the rationale that taxol could function as a cell-cycle selective radiosensitizer, we examined the consequences of combined drug-radiation exposures on the human grade 3 astrocytoma cell line, G18. Survival curve analysis shows a dramatic interaction between taxol and ionizing radiation with the degree of enhanced cell killing dependent on taxol concentration and on the fraction of cells in the G2 or M phases of the cell cycle. The sensitizer enhancement ratio (SER) for 10 nM taxol at 10% survival is approximately 1.8. These results obtained with cycling aerated radioresistant brain tumor cells indicate that significant advantage may derive from appropriate time-concentration dependent interactions in combined modality protocols.
Tishler
R B
RB
Department of Radiation Oncology, College of Physicians and Surgeons, Columbia University, New York, NY.
Schiff
P B
PB
Geard
C R
CR
Hall
E J
EJ
D000470:Alkaloids / Q000494:pharmacology*; D001254:Astrocytoma; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004341:Drug Evaluation; D006801:Humans; D007399:Interphase / Q000187:drug effects; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel