Taxol: a novel radiation sensitizer

Int J Radiat Oncol Biol Phys. 1992;22(3):613-7. doi: 10.1016/0360-3016(92)90888-o.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaloids / pharmacology*
  • Astrocytoma
  • Cell Survival / drug effects
  • Cell Survival / radiation effects
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Evaluation
  • Humans
  • Interphase / drug effects
  • Mitosis / drug effects
  • Paclitaxel
  • Radiation-Sensitizing Agents / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Alkaloids
  • Radiation-Sensitizing Agents
  • Paclitaxel