Induction TPF chemotherapy followed by CRT with fractionated administration of cisplatin in patients with unresectable locally advanced head and neck cancer

Background: In treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN), the use of docetaxel, cisplatin, and 5-fluorouracil (TPF) followed by high-dose cisplatin chemoradiotherapy (CRT) carries concerns over toxicity. We evaluated the feasibility of TPF as induction chemotherapy (IC) to Japanese patients and the tolerability of CRT with fractionated administration of cisplatin after IC. Methods: Patients with unresectable stage III, IV SCCHN received IC followed by CRT. IC consisted of three 3-week cycles of docetaxel 70–75 mg/m² on day 1, cisplatin 70–75 mg/m² on day 1, and 5-fluorouracil 750 mg/m² on days 1–5. Patients subsequently received IMRT concomitant with fractionated administration of cisplatin (20 mg/m²) on days 1–4, repeated every 3 weeks. The primary endpoint was completion of the three cycles of IC. Results: Forty-eight patients were enrolled. The IC treatment completion rate was 85%. Grade 3–4 toxicities of TPF were neutropenia (79%) and febrile neutropenia (15%). Thirty-eight patients (79%) achieved a response after IC. Forty patients subsequently underwent CRT. Thirty-three patients (83%) completed the planned cycles of fractionated administration of cisplatin, but seven (18%) did not. Grade 3–4 toxicities during CRT were neutropenia (23%), mucositis (53%), and dysphagia (33%). With a median follow-up of 36.1 months, 3-year overall survival was 65%. Conclusion: TPF IC is feasible and CRT with fractionated administration of cisplatin after IC is tolerable. IC followed by CRT appears to be a useful and safe sequential treatment. (Trial registration no. UMIN000024686).