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 (National Cancer Institute #7097)

Suresh S. Ramalingam, Chandra P. Belani, Philip Mack, Everett E. Vokes, Jeffrey Longmate, Ramaswamy Govindan, Marianna Koczywas, S. Percy Ivy, David R Gandara

Research output: Contribution to journalArticle

70 Scopus citations

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:Patients with SCLC with progression after prior platinum-based chemotherapy only; performance status (PS) of 0 to 2; and adequate bone marrow, renal, and hepatic function were included. The dose of cediranib was 45 mg PO once a day for the first 12 patients and was reduced to 30 mg PO once a day for the subsequent patients because of intolerance of the higher dose. Treatment was given on a daily continuous schedule. The primary end point was determination of the response rate. Results: Twenty-five patients were enrolled. Patient characteristics were as follows: 13 men; median age 61 years; PS 0 (12 pts), PS 1 (12 pts). A median of two cycles were administered. Salient grade 3/4 toxicities were fatigue, diarrhea, hypertension, proteinuria, and elevated liver enzymes. Tolerability was better with the 30 mg dose once a day. 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.

Original languageEnglish (US)
Pages (from-to)1279-1284
Number of pages6
JournalJournal of Thoracic Oncology
Volume5
Issue number8
DOIs
StatePublished - Aug 2010

Keywords

  • Angiogenesis
  • Biomarkers
  • Cediranib
  • Small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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