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Phase II Trial of Sorafenib in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Nasopharyngeal Carcinoma

Christine Elser, Lillian L. Siu, Eric Winquist, Mark Agulnik, Gregory R. Pond, Soo F. Chin, Peggy Francis, Robin Cheiken, James Elting, Angela McNabola, Dean Wilkie, Oana Petrenciuc, Eric X. Chen

From the Princess Margaret Hospital, University Health Network; Bayer Inc, Toronto; London Health Sciences Centre, London, Ontario, Canada; and Bayer Health Care, Bayer Research Center, West Haven, CT

Address reprint requests to Eric X. Chen, MD, PhD, Princess Margaret Hospital, University Health Network, Department of Medical Oncology and Hematology, 610 University Ave, Ste 5-719, Toronto, Ontario, Canada, M5G 2M9; e-mail: eric.chen{at}uhn.on.ca

Purpose To determine the efficacy and safety of single-agent sorafenib in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC).

Patients and Methods In this single-arm phase II trial, oral continuous sorafenib was administered in 28-day cycles. Patients had one line of chemotherapy for recurrent and/or metastatic disease, Eastern Cooperative Oncology Group performance status of 2, and adequate organ function. At the end of stage 1, efficacy criteria for further accrual were not met, but the study was amended to enroll an additional five patients for paired tumor biopsies.

Results Twenty-seven and 26 patients were eligible for toxicity and efficacy evaluations, respectively. One patient (3.7%; 95% CI, 0.1% to 19.0%) achieved a partial response. Disease stabilization was maintained in 10 patients (37.0%; 95% CI, 22.4% to 61.2%). The median time to progression was 1.8 months (95% CI, 1.6 to 3.4 months), and median overall survival time was 4.2 months (95% CI, 3.6 to 8.7 months). Sorafenib was well tolerated with few grade 3 and no grade 4 toxicities. Biomarker analysis of paired tumor samples before and after treatment with sorafenib revealed a decrease of pERK in all five patients, with a decrease in Ki67 in four patients, consistent with a disruption of ERK signaling. The antiapoptotic protein Mcl-1 was downregulated in four patients, and there was also evidence of antiangiogenic activity.

Conclusion Sorafenib was well tolerated and had modest anticancer activity comparable to monotherapy with other targeted agents in this group of patients. Further development in combination with radiation or other agents may be warranted.

Supported in part by Bayer Inc, Toronto, Ontario, Canada.

Presented in part at the 13th Annual European Cancer Conference, October 30-November 3, 2005, Paris, France; at the 41st Annual Meeting of the American Society of Clinical Oncology, May 13-17, 2005, Orlando, FL; and at the 18th European Organisation for the Research and Treatment of Cancer, National Cancer Institute, American Association for Cancer Research Symposium on Molecular Targets and Cancer Therapeutics, November 7-10, 2006, Prague, Czech Republic.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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