Neoadjuvant chemotherapy followed by concurrent hyperfractionated radiation therapy and sensitizing chemotherapy for locally advanced (T3–T4) oropharyngeal squamous cell carcinoma

Abstract

Radiation therapy (RT) is commonly used in the management of patients with advanced (T3-T4) oropharyngeal squamous cell carcinomas. In recent years, based upon the meta-analyses of randomized trials, chemotherapy administered concurrently with RT (chemoradiotherapy) has become the standard of care. Twice-a-day hyperfractionated or accelerated-fractionated RT regimens have been shown in a number of randomized trials to significantly improve the rate of local control compared with conventional once-a-day fractionation. Concurrent chemotherapy administered along with hyperfractionated or accelerated RT has been shown to add significant additional benefit over hyperfractionated or accelerated RT alone. Neoadjuvant chemotherapy (usually consisting of cisplatin and fluorouracil) also produces favorable responses in most patients (approximately 75% partial or complete response rates) with advanced head and neck cancer, but its role remains controversial. The results of treatment of 23 patients with T3 or T4 oropharyngeal squamous cell carcinomas who received neoadjuvant chemotherapy, followed by hyperfractionated RT (120 cGy twice-a-day to 74.4-76.8 Gy) were retrospectively reviewed. The 14 patients who were most recently treated also received concurrent sensitizing doses of single agent chemotherapy, usually cisplatin. No patient was seen with distant metastasis, and all were treated with curative intent. Ten patients had T3 and 13 patients had T4 primary tumors. Three patients (13%) had stage III disease and 20 patients (87%) had stage IV disease. Ten patients had base of tongue primaries, 12 had tonsillar primaries, and 1 had an oropharyngeal wall primary. Eighteen patients (78%) had clinically involved neck nodes. Seventy-four percent of patients had partial (>50%) or complete response at the primary site following neoadjuvant chemotherapy. One patient died of cardiorespiratory arrest after the first cycle. Thirteen percent of patients had unplanned interruptions of their RT courses secondary to severe mucositis. Local control at the primary site (minimum 2 years follow-up) was achieved in 17 of 19 (89%) patients. Two- and 5-year absolute survival rates were 71% and 55%, respectively. No patient was gastrostomy dependent beyond 18 months. Four patients developed neck failure after RT alone and none was successfully salvaged. This study is noteworthy in that it uses both neoadjuvant and concurrent sensitizing chemotherapy along with hyperfractionated RT. There is little information in the literature on this approach. Although the regimen is somewhat toxic, it is less so than many other regimens, which combined full-dose multiagent chemotherapy during the course of RT. The latter regimens also have a significant incidence of permanent dysphagia, gastrostomy dependence, and/or aspiration, complications that were not encountered in this group. The local control rate was high (89%). We continue to recommend this regimen for patients with locally advanced head and neck squamous cell carcinomas.