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Induction Chemotherapy followed by Concomitant TFHX Chemoradiotherapy with Reduced Dose Radiation in Advanced Head and Neck Cancer

¹ Department of Medicine, Section of Hematology/Oncology,
² Department of Radiation and Cellular Oncology,
³ Section of Otolaryngology/Head and Neck Surgery and
⁴ The Cancer Research Center, University of Chicago, Chicago, Illinois;
⁵ Departments of Medicine,
⁶ Radiation Oncology, and
⁷ Otolaryngology/Head and Neck Surgery and
⁸ The Cancer Research Center, Northwestern University, Chicago, Illinois; and
⁹ Departments of Medicine, Radiation and
¹⁰ Cellular Oncology, and
¹¹ Otolaryngology/Head and Neck Surgery University of Illinois, Chicago, Illinois

Purpose: Induction chemotherapy with carboplatin and paclitaxel followed by concomitant TFHX (paclitaxel, infusional 5-fluorouracil, hydroxyurea, and twice-daily radiation therapy administered every other week) has resulted in 70% 3-year survival in stage IV patients. Locoregional and distant control rates were 94 and 93%, respectively. In an attempt to decrease toxicity without compromising local control, a second cohort of patients was treated with a lower dose of radiation to sites of potential microscopic disease.

Experimental Design: Sixty-four patients were entered on study. Patients received six weekly doses of carboplatin (area under the curve 2) and paclitaxel (135 mg/m²) followed by five cycles of TFHX. The radiation dose to gross disease was 75 Gy as in the previous trial. The radiation dose to high-risk microscopic disease was reduced from 60 to 54 Gy, and the dose to low-risk microscopic disease was reduced from 45 to 39 Gy.

Results: Ninety-seven percent of patients had stage IV disease. The response rate to induction chemotherapy was 82% with a complete response rate of 42%. At the completion of therapy the clinical complete response rate rose to 100% with a median follow-up of 29 months. The actuarial 2 and 3-year survival was 77 and 70%, respectively. Five patients developed progressive disease for an overall 3-year progression-free survival of 90%. Two patients failed in locoregional sites alone, resulting in a 3-year locoregional control of 97%. The 3-year systemic control was 95%. Four patients were completely feeding tube dependent at the time of analysis. Only 1 of these patients had normal swallowing function before treatment.

Conclusions: In this second trial, induction chemotherapy with carboplatin and paclitaxel followed by TFHX chemoradiotherapy results in high survival and progression-free survival. The reduction in radiation dose did not compromise survival or disease control compared with our prior study using higher radiation doses. Data continues to support definitive evaluation of this approach.

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