Cediranib in patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium

Nicholas P. Campbell, Rangesh Kunnavakkam, Natasha Leighl, Mark D. Vincent, David R Gandara, Marianna Koczywas, Barbara J. Gitlitz, Edem Agamah, Sachdev P. Thomas, Walter M. Stadler, Everett E. Vokes, Hedy L. Kindler

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Introduction: Malignant mesothelioma (MM) is an aggressive disease with limited therapeutic options. In preclinical models, vascular endothelial growth factor (VEGF) stimulates MM proliferation. In MM patients, higher plasma VEGF levels correlate inversely with survival. Cediranib is an orally administered tyrosine kinase inhibitor of VEGF receptors-1, -2, and -3. Methods: We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed MM who had received ≤1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45. mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30. mg daily. Results: Fifty-one patients enrolled at 9 centers; 50 were evaluable for response. Partial responses were observed in 10% of patients; stable disease was seen in 34%. Disease control (PR. +. SD) was higher at the 45. mg cediranib dose level (67% vs. 34%, p= 0.04). Median progression-free survival was 1.8 months (95% CI 0.1, 14.2); median overall survival (OS) was 4.4 months (95% CI 0.9, 41.7). The 1-year survival rate was 15%. Grade 3/4 toxicities were more frequent in the 45. mg dose level group (87% vs. 43%, p= 0.002). These included fatigue, hypertension, pulmonary embolism, angioedema, and reversible posterior leukoencephalopathy. Median OS was superior in patients who developed ≥grade 3 hypertension (8.5 vs. 4.1 months, p= 0.024). Conclusion: This trial did not meet its pre-specified response endpoint. A higher cediranib dose level was associated with improved disease control, but this dose was poorly tolerated.

Original languageEnglish (US)
Pages (from-to)76-80
Number of pages5
JournalLung Cancer
Volume78
Issue number1
DOIs
StatePublished - Oct 2012

Keywords

  • Cediranib
  • Hypertension
  • Mesothelioma
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Campbell, N. P., Kunnavakkam, R., Leighl, N., Vincent, M. D., Gandara, D. R., Koczywas, M., Gitlitz, B. J., Agamah, E., Thomas, S. P., Stadler, W. M., Vokes, E. E., & Kindler, H. L. (2012). Cediranib in patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium. Lung Cancer, 78(1), 76-80. https://doi.org/10.1016/j.lungcan.2012.06.011