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Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation★

  • Clinical--patient studies
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Summary

Purpose

Because raised matrix metalloprotease (MMP) levels are associated with glioma invasion and angiogenesis, we tested the efficacy of marimastat (MT) an orally active drug that can reduce MMP levels, in patients with gliomas.

Patients and Methods

A total of 162 patients with intracranial glioblastoma multiforme or gliosarcomas who had undergone surgery and radiotherapy participated in this multicenter, double-blind, placebo-controlled, parallel group study conducted at 20 institutions. Seventy-nine patients (57 male, 22 female, median age 58 years) were randomized to receive placebo (PB), and 83 patients (51 male, 32 female, median age 57 years) were randomized to receive MT, 10 mg orally twice daily, until tumor progression.

Results

This intention-to-treat efficacy analysis showed no statistically significant difference between MT and PB groups with respect to survival (P=0.38, log rank test). The median survival time from protocol initiation was 37.9 weeks for the PB group and 42.9 weeks for the MT group, with a hazard ratio of 1.16 (95% CI 0.83 to 1.60). There were no statistically significant differences in quality of life between the PB and MT groups, as assessed by the FACT-BR questionnaire. Musculoskeletal toxicities led to dose modification or withdrawal in 20% of MT-treated and 1.2% of PB-treated patients.

Conclusion

MT does not improve survival in patients with glioblastoma or gliosarcoma following surgery and radiotherapy. Therefore, single-agent MT appears unwarranted; however, MT in combination with cytotoxic chemotherapy may be warranted, as suggested by observations in our study and other studies.

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Acknowledgement

We would like to thank Betty Notzon for editorial assistance and Melissa McLane for manuscript preparation.

Author information

Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Victor A. Levin & W.K. Alfred Yung

  2. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX , 77030, USA

    Gregory N. Fuller

  3. Department of Hematology-Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, 30322, USA

    Surasak Phuphanich

  4. Tom Baker Cancer Center, Calgary, Alberta, Canada

    Peter A. Forsyth

  5. Department of Neurosciences, Division of Neurosurgery, University of Western Ontario, London, Ontario, Canada

    Rolando Del Maestro

  6. Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada

    James R. Perry

  7. The Marimastat Glioblastoma Study Group* and British Biotech, Oxford, UK

    Mark Baillet

  8. Neuro-Oncology Unit 431, UT M. D. Anderson Cancer Center, P.O. Box 301402, Houston, TX , 77230-1402, USA

    Victor A. Levin

Authors
  1. Victor A. Levin
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  2. Surasak Phuphanich
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  3. W.K. Alfred Yung
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  4. Peter A. Forsyth
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  5. Rolando Del Maestro
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  6. James R. Perry
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  7. Gregory N. Fuller
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Corresponding author

Correspondence to Victor A. Levin.

Additional information

★This work was presented in part at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, on May 13, 2001, and supported by British Biotech Pharmaceuticals, Watlington Road, Oxford, OX4 6LY, UK. No author currently has a financial interest in Marimastat. Mark Baillet is currently with Origin Pharmaceutical Services Ltd.

*Participating institutions are listed in Table 1. Clinician authorship required ≥10 patient accrual from participating institution.

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Levin, V.A., Phuphanich, S., Alfred Yung, W. et al. Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation★ . J Neurooncol 78, 295–302 (2006). https://doi.org/10.1007/s11060-005-9098-5

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  • DOI: https://doi.org/10.1007/s11060-005-9098-5

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