Phase II study of cediranib (AZD 2171), an inhibitor of the vascular endothelial growth factor receptor, for second-line therapy of small cell lung cancer (NCI # 7097)

• Type of Material: Article
• Authors: Suresh S Ramalingam, Emory University; Chandra P. Belani, Penn State Hershey Cancer Institute; Philip C. Mack, University of California at Davis; Everett E. Vokes, University of Chicago Cancer; Jeffrey Longmate, City of Hope Cancer Center; Ramaswamy Govindan, Washington University; Marianna Koczywas, City of Hope Cancer Center; S. Percy Ivy, National Cancer Institute; David R. Gandara, University of California at Davis
• Language: English
• Date: 2010-08
• Publisher: Lippincott, Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2010 International Association for the Study of Lung Cancer
• Final Published Version (URL): http://journals.lww.com/jto/pages/articleviewer.aspx?year=2010&issue=08000&article=00026&type=abstract
• Title of Journal or Parent Work: Journal of Thoracic Oncology
• ISSN: 1556-0864
• Volume: 5
• Issue: 8
• Start Page: 1279
• End Page: 1284
• Grant/Funding Information: The study was supported by NCI N01-CM-62209, N01-CM-62201 & N01-CM-62205 and an ASCO Foundation Career Development Award to Suresh S. Ramalingam.; Division of Cancer Treatment : NCI
• Research Categories: Health Sciences, Oncology

Abstract

Background Inhibition of angiogenesis is a novel strategy for the treatment of cancer. We evaluated the safety and efficacy of cediranib, a potent small molecule inhibitor of the vascular endothelial growth factor receptor, in patients with refractory or recurrent small cell lung cancer (SCLC). Methods SCLC patients with progression following prior platinum-based chemotherapy only, performance status (PS) of 0-2 and adequate bone marrow, renal and hepatic function were included. The dose of cediranib was 45 mg PO QD for the first 12 patients, and was reduced to 30 mg PO QD for the subsequent patients due to intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary endpoint was determination of the response rate. Results Twenty five patients were enrolled. Patient characteristics: male 13; median age - 61; PS: 0 -12 pts, 1- 12 pts. A median of 2 cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria and elevated liver enzymes. Tolerability was better with the 30 mg QD dose. Nine patients had stable disease, but none had a confirmed partial response. The median progression-free survival and overall survival were 2 and 6 months respectively. Response criteria to proceed to full accrual were not met. Increase in circulating endothelial cell count was noted at the time of progression in several patients. Conclusions Cediranib failed to demonstrate objective responses in recurrent or refractory SCLC at the dose and schedule evaluated. The 45 mg dose was intolerable in a majority of SCLC patients.