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A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion

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Abstract

Malignant ascites and pleural effusion are challenging clinical problems, with a major impact on quality of life. We conducted a randomized phase II trial to assess the palliative value of cediranib, an oral vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). After a baseline paracentesis or thoracentesis (on day 0), patients with symptomatic malignant ascites and/or pleural effusion were randomized between immediate treatment with cediranib (Immediate Cediranib) or delayed treatment with cediranib (Delayed Cediranib) on day 29, or after a new puncture was needed. The primary objective of the study was the puncture-free survival, defined as the time from study start (day 1) to the first need for paracentesis or thoracentesis, or time to death, whichever event occurred first. Twelve patients were enrolled. The median puncture-free survival was 45 days (range 10–368) in the Immediate Cediranib patients and 7 days (range 4–13) in the Delayed Cediranib patients (P = 0.011). The change in puncture-free interval (the puncture-free survival after study start minus the puncture-free interval before study start) increased with a median of 31 days in the Immediate Cediranib patients and shortened with a median of 3 days in the Delayed Cediranib patients (P = 0.015). The most common adverse events were fatigue and anorexia. In conclusion, cediranib increased the puncture-free survival and puncture-free interval with an acceptable toxicity profile. This is the first study in which an oral VEGFR TKI showed beneficial palliative effects in patients with malignant effusions.

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Acknowledgments

The authors thank all the patients for participating in this study and acknowledge the statistical contributions of Rogier A.R.T. Donders and the assistance with patient-management of Michiel Kerkkamp and Mirjam G.W. Arens-van der Logt.

Funding

Cediranib was provided by AstraZeneca for this investigator-initiated study. Funding for this study was provided by the Dutch Cancer Society and the Dr. Paul Speth Foundation.

Conflict of Interest

None

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Authors and Affiliations

  1. Department of Medical Oncology 452, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    S. F. Mulder, M. J. Boers-Sonderen & C. M. L. van Herpen

  2. Department of Pulmonology, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    H. F. M. van der Heijden

  3. Department of Anesthesiology, Pain and Palliative Medicine, Radboud University Medical Centre, PO Box 9101, 6500 HB, Nijmegen, The Netherlands

    K. C. P. Vissers

  4. Department of Medical Oncology, Academic Medical Center, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    C. J. A. Punt

Authors
  1. S. F. Mulder
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  2. M. J. Boers-Sonderen
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  3. H. F. M. van der Heijden
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  4. K. C. P. Vissers
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  5. C. J. A. Punt
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  6. C. M. L. van Herpen
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Correspondence to S. F. Mulder.

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Mulder, S.F., Boers-Sonderen, M.J., van der Heijden, H.F.M. et al. A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion. Targ Oncol 9, 331–338 (2014). https://doi.org/10.1007/s11523-014-0306-0

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  • DOI: https://doi.org/10.1007/s11523-014-0306-0

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