Head and neck cancer is a major cause of
cancer-related deaths. In general, early stage head and
neck cancers are effectively treated with either radiation or surgery. More advanced
tumors often require
combined-modality therapy with both
radiation therapy and surgery. Recent investigations indicate that the addition of
chemotherapy may be helpful. One of the newer
chemotherapy agents that appears to have significant activity against
head and neck cancer is
paclitaxel (
Taxol; Bristol-Myers Squibb Company, Princeton, NJ).
Paclitaxel, originally derived from the western yew Taxus brevifolia, acts by increasing the stability of microtubules and preventing mitosis. Recent evidence indicates that the microtubule system is vital to the release of various
cytokines and that modulation of
cytokine release may play a major role in the
drug's antitumor activity. We report a phase II trial of
paclitaxel in patients with
head and neck cancer, not only to evaluate its clinical effects, but also to study its effect on
cytokine release. We assessed
interleukin-1 beta (IL-1 beta) and
tumor necrosis factor-alpha production by using a sensitive
enzyme-linked
immunosorbent assay to assess the serum of patients receiving
paclitaxel and to detect
cytokine release in vitro. The objective response rate was 36%, with 12% complete responses and 24% partial responses. No
IL-1 beta or
tumor necrosis factor-alpha was detected in patient serum at any time during the infusion of
paclitaxel or after overnight incubation with patient monocytes. No proIL-1 beta was detected in in vitro cultures of
paclitaxel-treated patient monocytes. When monocytes were stimulated with
endotoxin,
IL-1 beta production was greatest at 48 hours, suggesting that
paclitaxel can prime cells to produce greater quantities of
cytokines after a second stimulus.