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Phase II and Biologic Study of Interferon Alfa, Retinoic Acid, and Cisplatin in Advanced Squamous Skin Cancer

From the Departments of Thoracic/Head and Neck Medical Oncology, Diagnostic Imaging, Biostatistics, Head and Neck Surgery, and Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, Houston, TX, and Division of Medical Oncology, Johns Hopkins Oncology Center, Baltimore, MD.

Address reprint requests to Scott M. Lippman, MD, Departments of Thoracic/Head and Neck Medical Oncology and Clinical Cancer Prevention, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 236, Houston, TX 77030-4095; email: slippman{at}mdanderson.org

PURPOSE: The purpose of this study was to test interferon alfa (IFN), 13-cis-retinoic acid (13cRA), and cisplatin biochemotherapy in advanced squamous cell carcinoma (SCC) of the skin.

PATIENTS AND METHODS: Patients with advanced skin SCC received IFN (5 x 10⁶ IU/m², subcutaneous injection, three times a week), 13cRA (1 mg/kg, orally, daily), and cisplatin (20 mg/m², intravenous injection, weekly) in a phase II trial. The growth inhibition, cell-cycle, and apoptosis activity of these agents was evaluated in two skin SCC cell lines (SRB1-m7 and SRB12-p9).

RESULTS: Thirty-nine patients were enrolled. All were assessable for survival, 35 for response and toxicity (median follow-up was 38 months). The overall and complete response rates were 34% and 17%, respectively, with median durations of 9 and 35.4 months, respectively. The response rate was higher in locally advanced (67%) than metastatic (17%) disease (P = .007). Median survival was 14.6 months. One-, 2-, and 5-year survival rate estimates were 58%, 32%, and 21%, respectively. Toxicity included generally mild to moderate fatigue and mucocutaneous dryness, moderate to severe neutropenia (38%), and neutropenic fever (6%). There were no treatment-related deaths. In vitro growth inhibition and apoptosis effects of cisplatin were differential and inversely associated with those of retinoic acid and especially IFN in two skin SCC lines.

CONCLUSION: The rising incidence, morbidity, and mortality of advanced skin SCC are a major challenge for clinical oncologists. Combined 13cRA, IFN, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, non–cross-resistant biologic effects in vitro, which may account for the combination’s clinical activity.

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