Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
- Department of Medical Oncology, Instituto Nacional de Cancer, Rio de Janeiro (Brazil)
- Department of Head and Neck Surgery, Instituto Nacional de Cancer, Rio de Janeiro (Brazil)
- Department of Radiation Oncology, Instituto Nacional de Cancer, Rio de Janeiro (Brazil)
- Universidade de Sao Paulo, Faculdade de Medicina, Sao Paulo (Brazil)
- Clinical Research Division, Instituto Nacional de Cancer, Rio de Janeiro (Brazil)
- Medical Research, Roche Laboratories, Sao Paulo (Brazil)
- University of Washington, Seattle, WA (United States)
Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.
- OSTI ID:
- 21437997
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 3; Other Information: DOI: 10.1016/j.ijrobp.2009.08.079; PII: S0360-3016(10)00008-8; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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ANTINEOPLASTIC DRUGS
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