1. Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.
- Author
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Seiwert TY, Melotek JM, Blair EA, Stenson KM, Salama JK, Witt ME, Brisson RJ, Chawla A, Dekker A, Lingen MW, Kocherginsky M, Villaflor VM, Cohen EE, Haraf DJ, and Vokes EE
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell diagnosis, Carcinoma, Squamous Cell pathology, Disease-Free Survival, Female, Head and Neck Neoplasms diagnosis, Head and Neck Neoplasms pathology, Humans, Induction Chemotherapy, Male, Middle Aged, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local pathology, Radiotherapy Dosage, Squamous Cell Carcinoma of Head and Neck, Survival Rate, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Carcinoma, Squamous Cell therapy, Cetuximab administration & dosage, Chemoradiotherapy methods, Dose Fractionation, Radiation, Head and Neck Neoplasms therapy, Neoplasm Recurrence, Local prevention & control
- Abstract
Purpose: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation., Methods and Materials: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%., Results: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients., Conclusions: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation., (Copyright © 2016. Published by Elsevier Inc.)
- Published
- 2016
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