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Gefitinib in Patients with Malignant Mesothelioma: A Phase II Study by the Cancer and Leukemia Group B

¹ Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; ² Division of Medical Oncology and ³ Department of Medicine, University of Minnesota, Minneapolis, Minnesota; Departments of⁴ Biostatistics and Bioinformatics and ⁵ Pathology, Duke University, Medical Center, Durham, North Carolina; ⁶ Division of Medical Oncology, Medical University of South Carolina, Charlston, South Carolina; and ⁷ Department of Medicine, University of Chicago, Chicago, Illinois

Requests for reprints: Ramaswamy Govindan, Division of Medical Oncology, Washington University School of Medicine, 4960 Children's Place, Suite 108, St. Louis, MO 63110. Phone: 314-362-4819; Fax: 314-362-7086; E-mail: rgovinda{at}im.wustl.edu.

Purpose: The Cancer and Leukemia Group B conducted a phase II study of gefitinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, in patients with previously untreated malignant mesothelioma.

Experimental Design: Eligible patients had unresectable pleural or peritoneal mesothelioma, measurable disease, no prior therapy, and performance status 0-1 by Cancer and Leukemia Group B criteria. Gefitinib (500 mg p.o.) was administered once a day for 21 days. Patients underwent restaging after every two cycles. Therapy was continued until disease progression or unacceptable toxicity.

Results: The most common grade 3 toxicities were diarrhea (16%) and nausea (12%). Of 43 patients enrolled, 1 patient (2%) had a complete response, 1 patient (2%) had a partial response, 21 (49%) had stable disease lasting two to eight cycles, 15 (35%) had progressive disease, and 5 (12%) had early deaths. One-year survival was 32% [95% confidence interval (CI), 21-50%]. Median survival and failure-free survival were 6.8% (95% CI, 3.5-10.3) and 2.6 months (95% CI, 1.5-4.0), respectively. The 3-month failure-free survival was 40% (95% CI, 25-56%). EGFR expression score by immunohistochemistry done in 28 patients was categorized as low (EGFR 1+ or 2+) or high (EGFR 3+) expression: 97% had EGFR overexpression (2+ or 3+). The median and 3-month failure-free survival were 3.6 months and 40% for those patients with low EGFR expression compared with 8.1 and 40% for those with high EGFR expression.

Conclusions: Although 97% of patients with mesothelioma had EGFR overexpression, gefitinib was not active in malignant mesothelioma. EGFR expression does not correlate with failure-free survival.

Key Words: Gefitinib • EGFR • malignant mesothelioma

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