The targeted therapies erlotinib and cetuximab, in combination with standard chemotherapy regimens, are well tolerated and have very encouraging activity in recurrent/metastatic head and neck squamous cell carcinoma, according to two presentations at the American Society of Clinical Oncology (ASCO) 2007 Annual Meeting in Chicago.
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February 2008Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers, and preclinical data have demonstrated possible synergy with platinums and taxanes, said Edward S. Kim, MD, Assistant Professor of Thoracic/Head and Neck Medical Oncology at the University of Texas M. D. Anderson Cancer Center in Houston. Treatment options for recurrent/metastatic head and neck squamous cell carcinoma are limited.
An M. D. Anderson study of cisplatin and docetaxel showed a response rate of 40% and median survival of 9.6 months. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as a single agent in head and neck squamous cell carcinoma. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel, and erlotinib in advanced head and neck squamous cell carcinoma, Dr. Kim said.
In this open-label, Phase II trial, patients were required to have adequate performance status, measurable disease, and no prior EGFR therapy, and may have received prior induction, concomitant, or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx.
Treatment included docetaxel at 75 mg/m2 and cisplatin at 75 mg/m2, given intravenously every three weeks for up to six cycles and erlotinib at 150 mg, given orally, daily until progression. All agents were started on the first day, and patients were treated with growth factor support.
The trial has completed accrual of 50 patients, and 47 patients, median age of 57, were available for analysis. The majority had an Eastern Cooperative Oncology Group performance status of 1 (41 patients). Most patients (63%) had locoregional disease. The patients were predominantly smokers, with more than 75% being current or former smokers.
Prior therapy included radiation alone in four patients, surgery and radiation in 20, chemotherapy and radiation in five, and chemotherapy, radiation, and surgery in 13 patients. Six patients were untreated.
Complete responses have been observed in four patients (8%), partial responses in 28 patients (58%), and 13 patients (25%) have stable disease, for an overall response rate of 66% and a disease control rate of 91%. Only three patients had disease progression after two cycles of treatment.