A phase II trial of gefitinib in patients with chemosensitive and chemorefractory relapsed neuroendocrine cancers. A Hoosier Oncology Group Trial

Abstract

7160 Background: Gefitinib (Iressa) has demonstrated activity in patients (pts) with NSCLC. Tumor responses occurred in pts predominantly with adenocarcinoma, but responses have been observed in all histologies and regardless of the number of prior therapies. However, prior clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the EGFR. Although, EGFR is not over-expressed in SCLC, we postulated that gefitinib might affect tumor growth through other mechanisms. Methods: The primary objective was to assess the clinical control rate (CR, PR and SD > 90 days) of gefitinib in pts with chemoresistant and chemosensitive neuroendocrine tumors. Pts were to be recruited to the second stage if the disease control rate was 40% and 30% in chemo-sensitive or chemoresistant patients, respectively. Eligibility criteria included pathologic proof of a neuroendocrine tumor, ECOG PS 0–2, prior treatment with one or two prior chemotherapy regimens, and adequate end-organ function. Pts received gefitinib, 250 mg po daily until PD or intolerable side effects. Results: From April 2003 to March 2004, 19 pts were enrolled. Small cell lung cancer (SCLC) accounted for 18 of the 19 pts. 12 pts (63%) had chemosensitive disease, 7 (37%) had chemorefractory disease, 13 (68%) had one prior chemotherapy regimen and 6 (32%) had two prior chemotherapy regimens. Other pt characteristics: mean age 64 years (52–79); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in 3 pts (15.8%), pulmonary toxicities in 3 pts (15.8%), and one pt (5.3%) each with hyperglycemia or pain. Four pts had grade 4 toxicities: one pt (5.3%) with fatigue and 3 pts (15.8%) with dyspnea. There were no pts with grade 3 or 4 rash or diarrhea. Two pts had stable disease (<90 days) and 17 had progressive disease. The continuing criterion for stage one was not met and therefore stage 2 was not performed. Median TTP was 50 days (95% CI = 21–58 days). One year OS was 21% (95% CI = 6–45.6%). Conclusions: Although gefitinib has activity in pts with NSCLC, this study failed to demonstrate activity in pts with SCLC. Further studies of this agent in SCLC are not warranted at this time. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca AstraZeneca AstraZeneca