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Paul M. Harari, MD; Lorenzo Contreras; Michael A. Pickart; Mark A. Ritter, MD, PhD; Timothy J. Kinsella, MD

Arch Otolaryngol Head Neck Surg. 1993;119(7):738-742.

Abstract
• Objective.
—Proliferation of tumor clonogens during a course of conventional head and neck radiotherapy serves to compromise ultimate tumor control. Biologic strategies that attempt to alter tumor proliferation kinetics using cytostatic or antiproliferative agents may therefore prove valuable by limiting tumor cell repopulation during therapy.

Design.
—Three human squamous cell carcinoma (SCC) cell lines, derived from primary head and neck cancers, have been characterized in vitro via flow cytometric analysis of proliferation kinetics, and in vivo via tumor xenograft growth evaluation in athymic mice.

Results.
—The antiproliferative agent -difluoromethyl-ornithine (DFMO), an inhibitor of polyamine biosynthesis, induced growth inhibition of these SCCs in culture and when administered orally to athymic mice harboring SCC tumor xenografts. Cell cycle kinetic analysis via flow cytometry revealed that DFMO induced a lengthening of in vitro tumor cell potential doubling times. Similarly, DFMO administered continuously via the drinking water to athymic mice harboring human SCC xenografts induced a prolongation of in vivo tumor volume doubling.

Conclusions.
—These data indicate that biologic agents, such as DFMO, can alter SCC growth kinetics and may prove useful in designing new therapeutic strategies for rapidly proliferating tumors such as those that occur in the head and neck.

(Arch Otolaryngol Head Neck Surg. 1993;119:738-742)

Author Affiliations
From the Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison.

Footnotes
Accepted for publication December 30, 1992.

Presented at the Third International Conference on Head and Neck Cancer, San Francisco, Calif, July 26, 1992.

Reprint requests to Department of Human Oncology, K4/B100, University of Wisconsin Hospital and Clinics, 600 Highland Ave, Madison, Wl 53792 (Dr Harari).

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