Phase II study of cediranib in patients with malignant pleural mesothelioma: SWOG S0509

J Thorac Oncol. 2011 Nov;6(11):1938-45. doi: 10.1097/JTO.0b013e318229586e.

Abstract

Introduction: Malignant pleural mesothelioma (MPM) tumors express vascular epithelial growth factor (VEGF) and VEGF receptors. We conducted a phase II study of the oral pan-VEGF receptor tyrosine kinase inhibitor, cediranib, in patients with MPM after platinum-based systemic chemotherapy.

Methods: Patients with MPM previously treated with a platinum-containing chemotherapy regimen and a performance status 0 to 2 were eligible for enrollment. Cediranib 45 mg/d was administered until progression or unacceptable toxicity. The primary end point was response rate. Tumor measurements were made by RECIST criteria, with a subset analysis conducted using modified RECIST. A two-stage design with an early stopping rule based on response rate was used.

Results: Fifty-four patients were enrolled. Of 47 evaluable patients, 4 patients (9%) had objective responses, 16 patients (34%) had stable disease, 20 patients (43%) had disease progression, 2 patients (4%) had symptomatic deterioration, and 1 patient (2%) had early death. The most common toxicities were fatigue (64%), diarrhea (64%), and hypertension (70%); 91% of patients required a dose reduction. Median overall survival was 9.5 months, 1-year survival was 36%, and median progression-free survival was 2.6 months.

Conclusion: Cediranib monotherapy has modest single-agent activity in MPM after platinum-based therapy. However, some patient tumors were highly sensitive to cediranib. This study provides a rationale for further testing of cediranib plus chemotherapy in MPM and highlights the need to identify a predictive biomarker for cediranib.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Male
  • Mesothelioma / drug therapy*
  • Mesothelioma / mortality
  • Mesothelioma / pathology
  • Middle Aged
  • Neoplasm Staging
  • Pleural Neoplasms / drug therapy*
  • Pleural Neoplasms / mortality
  • Pleural Neoplasms / pathology
  • Prognosis
  • Quinazolines / administration & dosage*
  • Survival Rate

Substances

  • Quinazolines
  • cediranib

Grant support