Phase II and biologic study of interferon alfa, retinoic acid, and cisplatin in advanced squamous skin cancer

Dong M. Shin, Bonnie S. Glisson, Fadlo R. Khuri, John L. Clifford, Gary Clayman, Steven E. Benner, Arlene A. Forastiere, Lawrence Ginsberg, Diane Liu, J. Jack Lee, Jeffrey Myers, Helmuth Goepfert, Reuben Lotan, Waun Ki Hong, Scott M. Lippman

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: The purpose of this study was to test interferon alfa (IFNα), 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 IFNα (5 × 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 SRB 12-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 IFNα 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, IFNα, and cisplatin was clinically active in extensive locally advanced disease. Each agent had independent, noncross-resistant biologic effects in vitro, which may account for the combination's clinical activity.

Original languageEnglish (US)
Pages (from-to)364-370
Number of pages7
JournalJournal of Clinical Oncology
Volume20
Issue number2
DOIs
StatePublished - Jan 15 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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