Survival, tumor control, and toxicity with TPF before accelerated radiotherapy potentiated with cetuximab for stage III-IV unresectable head and neck cancer: A phase II study.

Abstract

5552^ Background: Concomittant cisplatin based chemoradiotherapy (CHRT) improves locoregional control compared to radiotherapy (RT) alone but with modest impact on survival. Toxicity is substantial. Neoadjuvant chemotherapy, now studied for CHRT, should augment toxicity further. The present phase II study explores TPF given before RT with the cytostatic component replaced by cetuximab (C) with the hypothesis of reasonable toxicity and potentially improved tumor control. Methods: Patients (pts) with untreated stage III-IV M0, WHO 0-1, unresectable squamous cell carcinoma of the oral cavity, oropharynx, larynx and hypopharynx were scheduled for 2 cycles of TPF (docetaxel and cisplatin 75mg/m2 day 1, 5-FU 1,000/m2 96 hours CI) every 3 weeks followed by RT (68Gy/4.5 weeks) with C given one week before (400mg/m2) and weekly during RT (250mg/m2). Brachytherapy (BT) of 8-15 Gy completed RT for oral and oropharyngeal tumors (except tonsillar T1-2). Neck dissection was considered for N2-3 disease. Tumor response was evaluated according to RECIST with CT, MRI or PET/CT before RT and 6 weeks follow up (FU). Toxicity (CTC 3.0) and QL (EORTC QLQ 30) was registered during and after treatment. Results: From 070401 to 090731 90 pts were enrolled in the study and were analysed 1 year FU. Median age 58, males 72, oral cavity 9, oropharynx 58, larynx 10, hypopharynx 13, stage IV disease 76 , (T4 22, T4N+ 15). Remission after TPF: CR 8, PR 44, SD 26 and PD 1, not evaluated 11 (off study 2) toxicity (acute): TPF cycles delayed 3, reduced 25, toxicity grade 5= 1 /90 pts (sepsis); cetuximab cycles delayed 18, reduced 10, grade 3 hypersensitivity reaction 3/90, grade 3 neck dermatitis 3/90 pts. Alive NED 1 year FU 77/90pts (86%), lost FU 2, DoD 7, dead intercurrent 2 (sepsis 1, pancreatic ca 1), alive with disease 2. Kaplan-Meier curves for locoregional control, disease-free and overall survival will be presented. Toxicity (1 year): 4 pts; grade 3 dysphagia 2 (1 PEG), fatigue 1, esophagitis 1. Conclusions: Neoadjuvant TPF can be given before bioradiotherapy with manageable, mostly acute toxicities. Antitumor effects are promising.