Abstract
Squamous cell carcinoma of the head and neck is the fourth most common cancer in the United States, and therapy for very advanced cases is relatively ineffective. Paclitaxel has activity against cancers of the breast, lung, prostate, cervix, and ovary. The activity of paclitaxel for squamous cell carcinoma of the head and neck is less certain, and results of its radiosensitization properties have been variable.
The radiation responses of two squamous carcinomas, SCC-9 (oropharynx) and HEP-2 (larynx), were examined to determine the radiosensitizing potential of paclitaxel. In vitro exposures for 24 and 48 h with paclitaxel concentrations of 10-4 to 6 × 10-2 µg/ml were followed by irradiation of 0.1–10 Gy. Percent survival was calculated by colony count, and the paclitaxel-radiation interaction was quantitated by the median effect principle and the combination index method of Chou and Talalay.
The paclitaxel-radiation combination resulted in multiphasic interactions in both 24 and 48 h paclitaxel pretreatment in SCC-9 and HEP-2 cell lines. In general there was slight synergism [combination index (CI) <1] at low dose-low effect levels (e.g., at a paclitaxel concentration of 0.002 µg/ml or lower and radiation of 0.1–0.3 Gy), moderate antagonism (CI >1) at median dose ranges and strong synergism (CI ≪1) at high dose ranges (e.g., at a paclitaxel concentration of 0.012–0.06 µg/ml and radiation doses of 3–10 Gy), especially at a surviving fraction of <0.1, which is therapeutically relevant.
The median effect principle and combination index method provided a simple way to quantitate the synergism or antagonism of a paclitaxel-radiation interaction under various conditions. This analysis demonstrated that paclitaxel-radiation synergy exists at doses that are readily achievable in the clinical scenario for both agents and that greater synergy occurred at high dose-high effect levels. These results suggest that the combination of both therapies should be explored further in clinical trials assessing the treatment of squamous cell carcinomas of the head and neck.
Footnotes
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↵1 This work was supported by NIH Grant 1 P 30 CA 46934-08, NIH Grant 1 P 50 CA 58187-01, Bristol-Myers Squibb Co., and the Elsa U. Pardee Foundation.
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↵2 To whom requests for reprints should be addressed, at Department of Radiation Oncology, Swedish Medical Center, 799 East Hampden #100, Englewood, CO 80110.
- Received February 13, 1996.
- Accepted September 19, 1996.
- ©1996 American Association for Cancer Research.
Volume 56, Issue 22
