Abstract
A randomized, multicenter, open-label, phase 3 study of patients with progressive, recurrent glioblastoma multiforme (GBM) for whom front-line therapy had failed was conducted. This study was designed to determine whether combination therapy with imatinib and hydroxyurea (HU) has superior antitumor activity compared with HU monotherapy in the treatment of recurrent GBM. The target population consisted of patients with confirmed recurrent GBM and an Eastern Cooperative Oncology Group performance status of 0–2 who had completed previous treatment comprising surgical resection, irradiation therapy, and first-line chemotherapy (preferably temozolomide (TMZ) containing regimen) and who have progressed despite treatment. If first-line chemotherapy did not contain TMZ, a second completed chemotherapy was acceptable. The primary efficacy parameter was progression-free survival (PFS). The primary comparison of combination therapy versus monotherapy for PFS was not significant (adjusted P = 0.56). The hazard ratio (HR) (adjusted HR = 0.93) was not clinically relevant. The median PFS for the combination arm was low at 6 weeks and similar to the median PFS in the monotherapy arm (6 weeks). The 6-month PFS for the two treatment groups was very similar (5% in the combination arm vs. 7% in the monotherapy arm). No clinically meaningful differences were found between the two treatment arms, and the primary study end point was not met. Among the patients receiving imatinib, no adverse events were reported that were either previously unknown or unexpected as a consequence of the disease.
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Acknowledgments
This paper has been submitted on behalf of all investigators and colleagues involved in the Ambrosia study. We are grateful to the following colleagues who agreed to act as investigators on the trial: Dr Erika Kettner MD, Staedtisches Klinikum, Magdeburg, Germany; Dr Kea Franz, MD, University Clinic, Frankfurt, Germany; Dr Marion Ritterodt, MD, Kliniken der Med. Hochschule, Hannover, Germany; Dr Sudarshan Selva-Nayagam, Royal Adelaide Hospital, Adelaide, Australia; Prof Klaus Koeffken, Friedrich-Schiller Universitaet, Jena, Germany; Prof A Sepehrnia, Clemenshospital, Muenster, Germany; Prof Bernhard Woermann, Staedisches Klinikum, Braunschweig, Germany; Prof Friedrich Weber, and Dr Ulrich Langenbach, Klinikum Saarbruecken, Saarbruecken, Germany; Dr Hartmut Döhner, University Clinic, Ulm, Germany. In addition to the above investigators, we wish to thank Steven Green, Novartis Pharma Basel, for excellent statistical support; Thierry Gorlia, EORTC, Brussels, for acting as Independent DMC statistician; Dr Martin van den Bent, Daniel den Hoed Oncology Center, Rotterdam, The Netherlands, Dr Alfred Yung, M.D. Anderson Cancer Center, Texas, USA, and Dr Riccardo Soffietti, Department of Neuroscience and Oncology, University of Turin, Italy, for being independent clinicians on DMC; and Dr Greg Sorensen, Massachusetts General Hospital, Boston, USA. We thank as well Dr David Reardon, Duke University Medical Center, North Carolina, USA, for his numerous valuable suggestions.
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Dresemann, G., Weller, M., Rosenthal, M.A. et al. Imatinib in combination with hydroxyurea versus hydroxyurea alone as oral therapy in patients with progressive pretreated glioblastoma resistant to standard dose temozolomide. J Neurooncol 96, 393–402 (2010). https://doi.org/10.1007/s11060-009-9976-3
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DOI: https://doi.org/10.1007/s11060-009-9976-3