Schedule-dependent radiation enhancement by paclitaxel with accelerated fractionated radiation in a human squamous carcinoma xenograft

Paclitaxel is a microtubule inhibitor that blocks cells in G2M, the most radiosensitive phase of the cell cycle. Thus paclitaxel may be therapeutically useful in combination with radiation. The purpose of this study was to determine whether paclitaxel in different schedules could enhance radiation-induced tumor regrowth delay in a human squamous cell carcinoma (FaDu) in nude mice. Tumors were exposed to accelerated fractionated radiation, in twice daily fractions of 2 Gy, over two 5-day periods. Paclitaxel was given intraperitoneally either as a single bolus or 10 daily boluses. While paclitaxel enhanced tumor regrowth delay when given within 30 min of the first daily radiation fraction in both drug schedules, it was more effective with daily paclitaxel, where tumor cures occurred at all doses. Even at the lowest daily bolus dose, where tumors did not respond to paclitaxel alone, the observed regrowth delay for the combined drug plus radiation treatment was much greater than expected from values for the drug and radiation treatments alone. These results suggest that paclitaxel enhances radiation-induced tumor regrowth delay in a more than additive manner, and may have clinical potential when combined with accelerated fractionated radiation in the treatment of solid tumors. Radiat. Oncol. Invest. 4:268–274, 1996.