Continued malignant cell proliferation in head and neck tumors during cytotoxic therapy

• Published in: Clinical cancer research 1996-09, Vol.2 (9), p.1453-1460
• Main Authors: H D Preisler, V M Kotelnikov, S LaFollette, S Taylor, 4th, S Mundle, N Wood, J S Coon, 4th, J Hutchinson, W Panje, D D Caldarelli, K Griem
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis - drug effects; Apoptosis - radiation effects; Biological and medical sciences; Biopsy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - therapy; Cell Count - drug effects; Cell Count - radiation effects; Cell Division - drug effects; Cell Division - radiation effects; Chemotherapy; Cisplatin - therapeutic use; Combined Modality Therapy; Female; Fluorouracil - therapeutic use; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Head and Neck Neoplasms - therapy; Humans; Immunohistochemistry; Male; Medical sciences; Middle Aged; Mouth Mucosa - drug effects; Mouth Mucosa - pathology; Mouth Mucosa - radiation effects; Paclitaxel - therapeutic use; Pharmacology. Drug treatments; S Phase; Time Factors
• ISSN: 1078-0432; 1557-3265

The effect of cytotoxic therapy on the proliferation of squamous cell carcinoma of the head and neck in vivo in patients was evaluated before and 15-35 days after the start of therapy. To accomplish this, iododeoxyuridine was administered at t = 0, and bromodeoxyuridine was administered 15-35 days later during treatment with a tumor biopsy obtained for study immediately after each pyrimidine infusion. Monoclonal antibodies specific for the halogenated pyrimidines were used to identify cells that were in the S-phase at the time of the infusions. Eleven patients were studied prior to treatment. Of those, the intratreatment biopsy of eight patients contained tumor tissue. In the other three patients, tumor tissue was not present in the second biopsy. Continued precursor 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 specimens tumor cells synthesizing DNA were not detected, and in four specimens the percentage of S-phase tumor cells was lower than that in the pretherapy specimen. Patients in whom there were no S-phase cells detected during treatment or in whom no tumor was detected in the second biopsy had a favorable treatment outcome in comparison to those patients in whom continued tumor proliferation during treatment was detected. The number of cells in S-phase prior to the initiation of treatment was not predictive of whether or not proliferation would continue during cytotoxic therapy. Evidence for reentry of kinetically quiescent cells into the cycle during treatment was noted. Additionally, cytotoxic therapy altered the proliferation pattern of normal-appearing mucosa as well. The results of this study demonstrate that tumor cell proliferation does continue in some squamous cell carcinoma of the head and neck during intensive cytotoxic therapy.