OSI-774 in advanced esophageal cancer: a phase II study

Abstract

4077 Background: Chemotherapy for advanced Esophageal Cancer (EC) has a response rate of 30–50% and there is no standard second-line regimen. Many ECs over express Epidermal Growth Factor Receptor (EGFR). The EGFR tyrosine kinase is inhibited by oral agent OSI-774, which has shown clinical activity with minimal toxicity in a number of solid tumors. Methods: Patients with measurable disease, treated with up to one prior chemotherapy regimen for metastatic disease (EGFR over expressing or non-over expressing by immunohistochemistry), are eligible. OSI-774 is given orally at 150mg daily, in 4-week cycles. Twenty-three patients (19 males, 4 females), ages 53–77 (mean 63.5), have been tested for EGFR status; 14 were EGFR over expressors (60%); 19 were adenocarcinomas, 4 were squamous histology. Eight patients were not treated (4 had deterioration before therapy, 2 were ineligible, 2 withdrew consent). Of the 15 treated, 11 had adenocarcinoma, 4 had squamous cancers. Ten patients (67%) were EGFR over expressors; Karnofsky Performance Status ranged from 70–100 (mean 80). Results: One confirmed partial response (EGFR+, squamous tumor, female, mediastinal lymph node disease) was observed after 2 cycles. The majority of patients (53%) progressed after one cycle. Two patients (13%) progressed during their second cycle and 3 (20%) progressed during a third cycle. One (EGFR+) maintained stable disease until he progressed after a sixth cycle (7%). No Grade 4 toxicities were seen. Three patients developed Grade 3 hepatic toxicity (2 had elevated alkaline phosphatase, 1 had elevated bilirubin and AST). Two patients had Grade 3 dermatologic toxicity (pustular skin rash) which resolved with antibiotics and dose reduction of OSI-774 to 100mg daily. Conclusions: OSI-774 appears to have activity in advanced esophageal carcinoma, with 1 of 15 pts (EGFR+, squamous histology) demonstrating a partial response. Accrual continues to identify the response rate of single agent OSI-774 in advanced EC. This study is supported in part by NCI Grant # NO1-CM17105. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Syntholabo