CONTINUED MALIGNANT-CELL PROLIFERATION IN HEAD AND NECK TUMORS DURINGCYTOTOXIC THERAPY

The effect of cytotoxic therapy on the proliferation of squamous cell carcinoma of the head and neck in vivo in patients was evaluated befor e and 15-35 days after the start of therapy. To accomplish this, iodod eoxyuridine was administered at t = 0, and bromodeoxyuridine was admin istered 15-35 days later during treatment with a tumor biopsy obtained for study immediately after each pyrimidine infusion. Monoclonal anti bodies specific for the halogenated pyrimidines were used to identify cells that were in the S-phase at the time of the infusions. Eleven pa tients were studied prior to treatment. Of those, the intratreatment b iopsy of eight patients contained tumor tissue. In the other three pat ients, tumor tissue was not present in the second biopsy. Continued pr ecursor incorporation into DNA-synthesizing cells during treatment was detected in six of eight tumor specimens. In two tumor specimens, an increase in the percentage of S-phase cells was noted, in two specimen s tumor cells synthesizing DNA were not detected, and in four specimen s the percentage of S-phase tumor cells was lower than that in the pre therapy specimen. Patients in whom there were no S-phase cells detecte d during treatment or in whom no tumor was detected in the second biop sy had a favorable treatment outcome in comparison to those patients i n whom continued tumor proliferation during treatment was detected. Th e number of cells in S-phase prior to the initiation of treatment was not predictive of whether or not proliferation would continue during c ytotoxic therapy. Evidence for reentry of kinetically quiescent cells into the cycle during treatment was noted. Additionally, cytotoxic the rapy altered the proliferation pattern of normal-appearing mucosa as w ell. The results of this study demonstrate that tumor cell proliferati on does continue in some squamous cell carcinoma of the head and neck during intensive cytotoxic therapy.