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Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1–3 newly diagnosed brain metastases

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Abstract

Patients with 1–3 brain metastases (BM) often receive sterotactic radiosurgery (SRS) without whole brain radiotherapy (WBRT). SRS without WBRT carries a high rate of relapse in the central nervous system (CNS). This trial used sunitinib as an alternative to WBRT for post-SRS adjuvant therapy. Eligible patients with 1–3 newly diagnosed BM, RTOG RPA class 1–2, received sunitinib after SRS. Patients with controlled systemic disease were allowed to continue chemotherapy for their primary disease according to a list of published regimens (therapy + sunitinib) included in the protocol. Patients received sunitinib 37.5 or 50 mg/days 1–28 every 42 days until CNS progression. Neuropsychological testing and MRIs were obtained every two cycles. The primary endpoint was the rate of CNS progression at 6 months (PFS6) after SRS. Fourteen patients with a median age of 59 years were enrolled. Primary cancers included lung 43 %, breast 21 %, melanoma 14 %. Toxicity included grade 3 or higher fatigue in five patients and neutropenia in two patients. The CNS PFS6 and PFS12 were 43 ± 14 and 34 ± 14 %, respectively. Of the ten patients who completed >1 neurocognitive assessment, none showed cognitive decline. Sunitinib after SRS for 1–3 BM was well tolerated with a PFS6 of 43 %. The prevention of progressive brain metastasis after SRS requires the incorporation of chemotherapy regimens to control the patient’s primary disease. Future trials should continue to explore the paradigm of secondary chemoprevention of BM after definitive local therapy.

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Funding

Pfizer Pharmaceuticals

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Authors and Affiliations

  1. Neurological Institute, Cleveland Clinic, Cleveland, OH, USA

    Manmeet S. Ahluwalia, Samuel T. Chao, Michael W. Parsons, John H. Suh, Cathy J. Brewer, Kathy N. Smolenski, Cathy Schilero, Lilyana Angelov, Gene H. Barnett, Michael A. Vogelbaum & David M. Peereboom

  2. Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA

    Manmeet S. Ahluwalia, Samuel T. Chao, John H. Suh, Cathy J. Brewer, Kathy N. Smolenski, Cathy Schilero, Matthew Rump, Paul Elson & David M. Peereboom

  3. Henry Ford Hospital, Detroit, MI, USA

    Ding Wang & Tom Mikkelsen

  4. Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Michael W. Parsons, Matthew Rump & Paul Elson

  5. Geisinger Medical Center, Danville, PA, USA

    Robert J. Weil

  6. Cleveland Clinic Lerner College of Medicine, The Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center, Solid Tumor Oncology, Cleveland Clinic, 9500 Euclid Ave. R35, Cleveland, OH, 44195, USA

    Manmeet S. Ahluwalia, Samuel T. Chao, John H. Suh, Cathy J. Brewer, Kathy N. Smolenski, Cathy Schilero, Lilyana Angelov, Gene H. Barnett, Michael A. Vogelbaum & David M. Peereboom

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  1. Manmeet S. Ahluwalia
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  2. Samuel T. Chao
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  3. Michael W. Parsons
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  4. John H. Suh
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  5. Ding Wang
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  8. Kathy N. Smolenski
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  9. Cathy Schilero
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  11. Paul Elson
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  13. Gene H. Barnett
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  16. David M. Peereboom
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Correspondence to David M. Peereboom.

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DMP, research funding Pfizer Pharmaceuticals

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Ahluwalia, M.S., Chao, S.T., Parsons, M.W. et al. Phase II trial of sunitinib as adjuvant therapy after stereotactic radiosurgery in patients with 1–3 newly diagnosed brain metastases. J Neurooncol 124, 485–491 (2015). https://doi.org/10.1007/s11060-015-1862-6

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  • DOI: https://doi.org/10.1007/s11060-015-1862-6

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