Results of the Southwest Oncology Group phase II evaluation (study S0031) of ZD1839 for advanced transitional cell carcinoma of the urothelium.

STUDY TYPE: Prognosis (inception cohort). LEVEL OF EVIDENCE: 1b. OBJECTIVE: To evaluate the epidermal growth factor receptor (EGFR)-targeted agent ZD1839 in patients who failed one previous chemotherapeutic regimen for metastatic transitional cell carcinoma (TCC), and to correlate patterns of response with the expression of EGFR. PATIENTS AND METHODS: Thirty-one patients with metastatic TCC of the urothelial tract were treated with ZD1839 500 mg oral daily. Patients were required to have a pretreatment biopsy to assess EGF expression. RESULTS: The median progression-free survival was 2 months, with only two patients (6.5%) surviving past 6 months with no disease progression. Thirty patients were evaluable for toxicity; there was grade 4 cerebrovascular ischaemia and an increase in creatinine level. All patients were evaluable for response, with one confirmed partial response (3%; 95% confidence interval, CI, 0-17%) in a patient with pulmonary metastases. All patients have died, and the estimated median (95% CI) survival is 3 (2-7) months. CONCLUSIONS: ZD1839 is ineffective as a second-line agent for urothelial carcinoma.