1. A Phase 1 Study of Afatinib in Combination with Postoperative Radiation Therapy with and Without Weekly Docetaxel in Intermediate- and High-Risk Patients with Resected Squamous Cell Carcinoma of the Head and Neck.
- Author
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Margalit DN, Haddad RI, Tishler RB, Chau NG, Schoenfeld JD, Bakst RL, Misiukiewicz KJ, Gupta V, Posner M, Hanna GJ, Mahmood U, Rawal B, Catalano PJ, Rath L, Bacay A, McHugh P, and Rabinowits G
- Subjects
- Adult, Afatinib adverse effects, Aged, Antineoplastic Agents adverse effects, Carcinoma, Squamous Cell pathology, Combined Modality Therapy adverse effects, Combined Modality Therapy methods, Diarrhea etiology, Disease-Free Survival, Docetaxel administration & dosage, Drug Administration Schedule, Female, Head and Neck Neoplasms pathology, Humans, Hypokalemia etiology, Male, Maximum Tolerated Dose, Middle Aged, Mouth Neoplasms therapy, Mucositis etiology, Postoperative Period, Prospective Studies, Radiotherapy Dosage, Afatinib administration & dosage, Antineoplastic Agents administration & dosage, Carcinoma, Squamous Cell therapy, Head and Neck Neoplasms therapy
- Abstract
Purpose: To determine the maximum tolerated dose and tolerability of (1) afatinib in combination with postoperative radiation therapy (PORT) for patients with intermediate-risk squamous cell carcinoma of the head and neck (SCCHN) and (2) afatinib in combination with PORT and weekly docetaxel for high-risk SCCHN., Methods and Materials: An open-label, multicenter, 2-cohort, phase 1 dose-escalation trial was conducted using a 3 + 3 design. Eligible patients had definitive surgery for SCCHN, including the oral cavity, oropharynx, larynx, or hypopharynx and had intermediate- or high-risk pathologic features. Afatinib was given for a 1-week lead in before PORT and daily during 6 to 6.5 weeks of PORT with or without weekly docetaxel. The starting dose was 30 mg and could be escalated to 40 mg or de-escalated to 20 mg. The primary objective was to determine the maximum tolerated dose of afatinib with PORT or PORT + docetaxel., Results: Between April 2013 and November 2017, 27 patients were enrolled and started study treatment, including 16 intermediate-risk patients and 11 high-risk patients, all with Eastern Cooperative Oncology Group performance status of 0 to 1. Most patients (n = 25) had oral cavity cancer and were treated to a median total dose of 60 Gy in the intermediate-risk arm and 65 Gy in the high-risk arm. There was 1 grade 4 event, but no deaths. The maximum tolerated dose was not established owing to dose-limiting toxicities (DLTs) in both arms. In the high-risk arm, DLTs were grade 3 mucositis (n = 3) and grade 3 diarrhea/hypokalemia (n = 1). In the intermediate-risk arm, DLTs were grade 3 mucositis (n = 4) and grade 3 diarrhea (n = 2)., Conclusions: Afatinib in combination with PORT for mucosal SCCHN was difficult to tolerate because of grade 3 toxicity, mostly mucositis, in a cohort of patients requiring high-dose PORT to the oral cavity. This regimen may be better tolerated for a non-oral cavity site or if given in a different schedule., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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