Induction Chemotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma

Abstract

Locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN), which accounts for 60% of all cases of head and neck cancer, has a poor prognosis, despite multidisciplinary treatment. Induction chemotherapy (ICT) has been developed since the 1980s. The purposes of ICT are (1) improvement of the survival rate and prognosis through suppression of distant metastasis, and (2) function-preserving (larynx-preserving) through tumor shrinkage. The current standard regimen for ICT is docetaxel plus CDDP plus 5-FU (TPF therapy). However, it is not clear whether ICT followed by chemoradiation therapy (ICT-CRT) might be superior to CRT alone. There is controversy about whether ICT-CRT can be safely implemented, especially because of the high rate of treatment-related deaths following TPF treatment. Therefore, paclitaxel (PTX) plus carboplatin (CBDCA) plus cetuximab (Cmab) (PCE) therapy as IC for unresectable LA-SCCHN was investigated in a multicenter trial in Japan. This ICT protocol consisted of CBDCA at AUC=1.5, PTX at 80 mg/m² and Cmab at an initial dose of 400 mg/m², followed by 250 mg/m², administered weekly for 8 weeks. Following this IC, CDDP (20 mg/m², 4 days × 3 cycles, cumulative CDDP dose: 240 mg/body) and concurrent radiotherapy (70 Gy/35 fr/7 weeks) were started. The primary endpoint was the rate of CRT completion. The percent (%) CRT completion was 96.9%. The response rate was 88.6% to the ICT and 93.8% after the CRT phase. The 3-year overall survival rate was 83.5%. The main grade 3 toxicities were neutropenia (11.4%) and skin rash (5.7%) during the ICT, and oral mucositis (31.3%) and neutropenia (12.5%) during the CRT. In conclusion, the new ICT regimen of PCE shows promising efficacy and is a promising regimen.