Journal of Clinical Oncology, Vol 18, Issue 8
(April), 2000: 1652-1661
© 2000 American Society for Clinical Oncology
Concomitant Chemoradiotherapy as Primary Therapy for Locoregionally Advanced Head and Neck Cancer
By Everett E. Vokes,
Merrill S. Kies,
Daniel J. Haraf,
Kerstin Stenson,
Marcy List,
Rod Humerickhouse,
M. Eileen Dolan,
Harold Pelzer,
Laura Sulzen,
Mary Ellyn Witt,
Yi-Ching Hsieh,
Bharat B. Mittal,
Ralph R. Weichselbaum
From the Departments of Medicine (Section of Hematology/Oncology)Radiation and Cellular Oncology, and Surgery, Committee of Clinical Pharmacology, and Comprehensive Cancer Center, University of Chicago, and Departments of Medicine, Radiation Oncology, and Surgery, and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL.
Address reprint requests to Everett E. Vokes, MD, University of Chicago, 5841 South Maryland Avenue, MC 2115, Chicago, IL 60637; email evokes{at}medicine.bsd.uchicago.edu
PURPOSE: To achieve locoregional control of head and neck cancer, survival, and organ preservation using intensive concomitant chemoradiotherapy.
PATIENTS AND METHODS: This study was a phase II trial of chemoradiotherapy with cisplatin 100 mg/m2 every 28 days, infusional fluorouracil 800 mg/m2/d for 5 days, hydroxyurea 1 g orally every 12 hours for 11 doses, and radiotherapy twice daily at 1.5 Gy/fraction on days 1 through 5 (total dose, 15 Gy). Five days of treatment were followed by 9 days of rest, during which time patients received granulocyte colony-stimulating factor. Five cycles (three with cisplatin) were administered over 10 weeks (total radiotherapy dose,  75 Gy). Adjuvant chemoprevention with retinoic acid and interferon alfa-2A was offered.
RESULTS: Seventy-six patients were treated (stage IV, 93%; N2, 54%; N3, 21%). At a median follow-up of 38 months, the 3-year progression-free survival is 72%, locoregional control 92%, systemic control 83%, and overall survival 55%. Toxicities included mucositis (grade 3, 45%; grade 4, 12%), neutropenia (grade 4, 39%), and thrombocytopenia (grade 4, 53%). Surgery at the primary site was performed in 13 patients, and 39 had neck dissection. A majority of patients declined adjuvant chemoprevention. Pharmacokinetic parameters were not prognostic of tumor control. Quality of life declined during treatment but returned from good to excellent by 12 months after treatment.
CONCLUSION: Intensive concomitant chemoradiotherapy leads to high locoregional control and survival rates with organ preservation and a reversal of the historical pattern of failure (distant > locoregional). Surgery after concomitant chemoradiotherapy is feasible. Compliance with adjuvant chemoprevention is poor. Identification of less toxic regimens and improved distant disease control emerge as important future research goals.
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