A Phase II Trial of Gefitinib (Iressa, ZD1839) in Stage IV and Recurrent Renal Cell Carcinoma

Purpose: The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomasand may play a role in tumor initiationand progression. Gefitinib(Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinibin advanced renal cell carcinoma. Experimental Design: Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status. Results: Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35–78 years); 17 males, 4 females; median performance status 0 (range 0–2); median number of prior systemic therapies 1 (range, 0–3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1–14+). The best responsewas stable disease in eight patients (38%). Median progression-free survivalwas 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value < 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease. Conclusions: Gefitinibis without significant conventional activity in renal cell carcinoma. The relation of “stable disease” to treatment or to disease-related prognostic heterogeneity remains to be defined.