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Weekly Carboplatin and Paclitaxel Followed by Concomitant Paclitaxel, Fluorouracil, and Hydroxyurea Chemoradiotherapy: Curative and Organ-Preserving Therapy for Advanced Head and Neck Cancer

Everett E. Vokes, Kerstin Stenson, Fred R. Rosen, Merrill S. Kies, Alfred W. Rademaker, Mary Ellyn Witt, Bruce E. Brockstein, Marcy A. List, Bing Bing Fung, Louis Portugal, Bharat B. Mittal, Harold Pelzer, Ralph R. Weichselbaum, Daniel J. Haraf

From the Department of Medicine, Section of Hematology/Oncology, Department of Radiation and Cellular Oncology, Section of Otolaryngology/Head and Neck Surgery and the Cancer Research Center, University of Chicago; the Departments of Medicine, Radiation Oncology, and Otolaryngology/Head and Neck Surgery and the Cancer Research Center, Northwestern University; the Departments of Medicine, Radiation and Cellular Oncology, and Otolaryngology/Head and Neck Surgery, University of Illinois, Chicago, IL.

Address reprint requests to: Everett E. Vokes, MD, University of Chicago, 5841 S. Maryland Ave, MC 2115, Chicago, IL 60637-1470; email: evokes{at}medicine.bsd.uchicago.edu.

Purpose: The paclitaxel, fluorouracil, and hydroxyurea regimen of paclitaxel, infusional fluorouracil, hydroxyurea, and twice-daily radiation therapy (TFHX) administered every other week has resulted in 3-year survival rates of 60% of stage IV patients. Locoregional and distant failure rates were 13% and 23%, respectively. To reduce distant failure rates, we added a brief course of induction chemotherapy to TFHX.

Patients and Methods: Sixty-nine patients received six weekly doses of carboplatin (AUC2) and paclitaxel (135 mg/m²) followed by five cycles of TFHX.

Results: Ninety-six percent had stage IV disease. Response to induction chemotherapy was partial response 52% and complete response (CR) 35%. Symptomatically, there was a significant reduction in mouth and throat pain. The most common grade 3 or 4 toxicity was neutropenia (36%). Best response following completion of TFHX was CR in 83%. Toxicities of TFHX consisted of grade 3 or 4 mucositis (74% and 2%) and dermatitis (47% and 14%). At a median follow-up of 28 months, locoregional or systemic disease progression were each noted in five patients. The overall 3-year progression-free survival was 80% (95% confidence interval [CI], 71% to 90%), and the 2- and 3-year overall survival rates were 77% (95% CI, 66% to 87%) and 70% (95% CI, 59% to 82%), respectively. At 12 months, five patients were completely feeding-tube dependent.

Conclusion: Administration of carboplatin and paclitaxel before TFHX chemoradiotherapy results in high response activity and may decrease distant failure rates. Overall survival, progression, and organ preservation/functional outcome data support definitive evaluation of this approach.

Supported in part by the University of Chicago/Northwestern University Oral Cancer Center (P50 DE11921-04), University of Chicago Cancer Research Center (P30 CA14599), The Francis Lederer Foundation, The Geraldi Norton Memorial Corporation, The Robert and Valda Svendsen Memorial, and Bristol-Myers Squibb, Princeton, New York.

Presented at the Annual Meetings of the American Society of Clinical Oncology in May 2000 in New Orleans, LA, and in May 2002 in Orlando, FL.

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