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Phase III Randomized Trial of Cisplatin Plus Placebo Compared With Cisplatin Plus Cetuximab in Metastatic/Recurrent Head and Neck Cancer: An Eastern Cooperative Oncology Group Study

From the Department of Internal Medicine, Yale University School of Medicine, New Haven, CT; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Department of Biostatistics, Harvard School of Public Health, Boston, MA; Division of Hematology/Oncology, Milton S. Hershey Medical Center, Hershey, PA; Cancer Center of Kansas, Wichita, KS; the Sidney Kimmel Cancer Center, Johns Hopkins University, Baltimore, MD

Address reprint requests to Barbara Burtness, MD, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111; e-mail: barbara.burtness{at}fccc.edu

PURPOSE: Therapy of recurrent/metastatic squamous cell carcinoma of the head and neck results in median progression-free survival (PFS) of 2 months. These cancers are rich in epidermal growth factor receptor (EGFR). We wished to determine whether the addition of cetuximab, which inhibits activation of EGFR, would improve PFS.

PATIENTS AND METHODS: Patients with recurrent/metastatic squamous cell carcinoma of the head and neck were randomly assigned to receive cisplatin every 4 weeks, with weekly cetuximab (arm A) or placebo (arm B). Tumor tissue was assayed for EGFR expression by immunohistochemistry. The primary end point was PFS. Secondary end points of interest were response rate, toxicity, overall survival, and correlation of EGFR with clinical end points.

RESULTS: There were 117 analyzable patients enrolled. Median PFS was 2.7 months for arm B and 4.2 months for arm A. The hazard ratio for progression of arm A to arm B was 0.78 (95% CI, 0.54 to 1.12). Median overall survival was 8.0 months for arm B and 9.2 months for arm A (P = .21). The hazard ratio for survival by skin toxicity in cetuximab-treated patients was 0.42 (95% CI, 0.21 to 0.86). Objective response rate was 26% for arm A and 10% for arm B (P = .03). Enhancement of response was greater for patients with EGFR staining present in less than 80% of cells.

CONCLUSION: Addition of cetuximab to cisplatin significantly improves response rate. There was a survival advantage for the development of rash. Progression-free and overall survival were not significantly improved by the addition of cetuximab in this study.

Supported in part by Public Health Service Grants No. CA23318, CA66636, CA21115, CA07190, and CA16116 from the National Cancer Institute, National Institutes of Health, and the United States Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute.

Presented in part at the 38th Annual Meeting of the American Society of Clinical Oncology, May 18-21, Orlando, FL, and the American Association for Cancer Research/National Cancer Institute/European Organisation for Research and Treatment of Cancer International Conference on Molecular Targets in Cancer Therapy, November 17-21, 2003, Boston, MA.

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

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