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Favorable outcome in the elderly cohort treated by concomitant temozolomide radiochemotherapy in a multicentric phase II safety study of 5-ALA

  • Clinical Study – Patient Study
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Abstract

The primary objective of this augmental, prospective, uncontrolled phase II multicentre trial was to assess adverse events (AE) associated with malignant glioma resection using 5-aminolevulinic (5-ALA). During accrual, the standard of adjuvant therapy changed to concomitant radiochemotherapy with adjuvant temozolomide (RT/TMZ). Thus, this study also provided a platform for investigating the influence of RT/TMZ on survival in patients with fluorescence-guided resections. Malignant glioma patients, aged 18–75 years and with a Karnofsky performance score (KPS) ≥70%, were eligible. Data were collected on adverse events, KPS, survival and adjuvant therapies. In 243 patients evaluable for safety, 6-week AE incidence was 51.9% (nervous system disorders: 30.0%). Three patients experienced four possibly drug-related AEs. Grade III/IV incidence was 18.9% (nervous system disorders: 10.7%). About 48 h after surgery, AE incidence was 26.3% (9.9% grade III/IV), which was related to overall survival. A total of 219 patients (glioblastoma 206; anaplastic astrocytoma: 13) qualified for efficacy analysis. Median overall survival was 14.1 months (95% CI: 12.0–16.6), but 16.3 (13–19.2) months in 122 glioblastoma patients receiving RT/TMZ compared to 11.9 (9.6–14.1) months in the remaining 84 patients (P = 0.0194). Older patients (≥60 years) had less adjuvant therapies than younger patients. Median survival of older glioblastoma patients with RT/TMZ was also significantly prolonged (16.3; 12.0–17.2 months vs. 11.2; 7.4–14.1, hazard ratio = 0.55; 0.32–0.92). Risks of surgery were similar to past experiences with 5-ALA. Ancillary analyses demonstrated surgical glioblastoma patients, including the elderly, to have derived benefit from RT/TMZ. Thus, older patients should not generally be excluded from accepted therapies (fluorescence-guided resection plus RT/TMZ).

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Authors and Affiliations

  1. Department of Neurosurgery, Westfälische-Wilhelms Universität, Albert Schweizer Street 33, Münster, Germany

    Walter Stummer

  2. Department of Neurosurgery, Universitätsklinikum Gießen und Marburg GmbH, Marburg, Germany

    Ulf Nestler

  3. Division of Neurosurgery, Chirurgische Universitätsklinik Rostock (AöR), Rostock, Germany

    Florian Stockhammer

  4. Klinik und Poliklinik für Neurochirurgie, Universitätsklinikum Carl Gustav Carus, TU Dresden, Dresden, Germany

    Dietmar Krex

  5. Klinik für Neurologie, BG-Kliniken Bergmannstrost, Halle, Germany

    Bodo C. Kern

  6. Department of Neurosurgery, Universitätsklinikum Schleswig–Holstein Campus Kiel, Kiel, Germany

    Hubert M. Mehdorn

  7. Department of Neurosurgery, University of Würzburg, Würzburg, Germany

    Giles H. Vince

  8. Medac Gesellschaft für Medizinische Spezialpräparate mbH, Wedel, Germany

    Uwe Pichlmeier

Authors
  1. Walter Stummer
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  2. Ulf Nestler
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  3. Florian Stockhammer
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  4. Dietmar Krex
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  5. Bodo C. Kern
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  6. Hubert M. Mehdorn
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  7. Giles H. Vince
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  8. Uwe Pichlmeier
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Corresponding author

Correspondence to Walter Stummer.

Additional information

Study collaborators are presented in the Appendix.

Appendix

Appendix

C. Woiciechowsky (Virchow-Klinikum der HU Berlin), M. Brock, T. Kombos, B. Kühn, C. Wille (Universitätsklinikum Benjamin Franklin, Berlin), J.-C. Tonn, C. Goetz (Universitätsklinikum München), V. Seifert, K. Franz (J.W. Goethe Universitätsklinikum, Frankfurt a. M.), W. Hassler, A. Bani, D. Klassen (Klinikum Duisbug gGmbH, Duisburg), F. Weber, U. Langenbach (Klinikum Saarbrücken), M. Westphal, O.W. Heese (Universitätsklinikum Hamburg-Eppendorf), T. Grumme, T. Stretz (Zentralklinikum Augsburg), D. Stolke, S. Asgari, B. El Hamalawi (Universitätsklinikum Essen), R. Steinmeier, S.-A. May, P. Duscha (Klinikum Chemnitz gGmbH, Chemnitz), U. Kehler, M. Kämper (Asklepios Klinik Altona, Hamburg), J. Meixensberger (Universitätsklinikum, Leipzig), B. Meyer, F. Ringel (Klinikum rechts der Isar der TU, München), M. Tatagiba, R. Ritz (Universitätsklinikum, Tübingen), H.-P. Richter, K. Seitz (Bezirkskrankenhaus, Universität Ulm, Günzburg), A. Unterberg (Ruprecht-Karls-Universität, Heidelberg), J. Zentner, J. Vesper, A. Weyerbrock (Albert-Ludwigs-Universität, Freiburg).

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Stummer, W., Nestler, U., Stockhammer, F. et al. Favorable outcome in the elderly cohort treated by concomitant temozolomide radiochemotherapy in a multicentric phase II safety study of 5-ALA. J Neurooncol 103, 361–370 (2011). https://doi.org/10.1007/s11060-010-0400-9

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  • DOI: https://doi.org/10.1007/s11060-010-0400-9

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