Rechallenge with temozolomide with different scheduling is effective in recurrent malignant gliomas

  • Authors:
    • H. M. Strik
    • J.-H. Buhk
    • A. Wrede
    • A. L. Hoffmann
    • H. C. Bock
    • M. Christmann
    • B. Kaina
  • View Affiliations

  • Published online on: November 1, 2008     https://doi.org/10.3892/mmr_00000042
  • Pages: 863-867
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Abstract

Treatment of recurrent malignant glioma, which has a poor patient prognosis, has not been standardised. Moreover, it is unclear whether repeated treatment with temozolomide is effective in patients who received previous temozolomide treatment before developing a recurrence. Here, we present the results of a high-dose individually adapted 21-day regimen demonstrating that rechallenge is effective even in patients expressing O6-methylguanine-DNA methyltransferase (MGMT) in the tumor. Twenty-one patients with recurrent malignant gliomas pre-treated with temozolomide, 18 WHO IV glioblastoma (GBM) and 3 WHO III patients, received 100 mg/m2 temozolomide on days 1-21/28. The GBM patients had a median Karnofsky performance status of 60% and a median age of 54.8 years. Blood counts decreased continuously, enabling a gradual dose adaptation. When blood counts dropped below normal values, temozolomide was applied on days 1-5/7. Dosage was reduced to 50-75 mg/m2 in 11 patients and gradually increased up to 130 mg/m2 in 3 patients. WHO grade 3/4 toxicity was hematological in 3 patients and non-hematological in 3 patients. In GBM patients (n=18), response after >3 months was complete in 3 patients, partial in 1 (22%), stable disease in 7 (39%) and progressive disease in 7 (39%). Progression-free survival at 6 months (PFS-6M) was 39%. Median survival was 9.1 months from relapse and 17.9 months overall. Of the patients with unmethylated MGMT promoter, 2/7 were progression-free for >6 (15 and 19) months. The data indicate that rechallenge with near-continuous, higher-dose temozolomide (100 mg/m2 on days 1-21/28 or days 1-5/7 with individual dose adaptation) is also feasible in patients with critical blood counts. Objective responses can be achieved even after relapse during a conventional 5/28-day regimen. The resistance of tumors characterized by unmethylated MGMT promoter may be overcome by near continuous temozolomide administration, which is probably most effective with a 5/7-day schedule. In spite of the relatively poor clinical prognosis, the data indicate that rechallenge with temozolomide with a dose-dense and long-lasting administration protocol is tolerable and comparable with other reported treatment protocols involving temozolomide.

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November 2008
Volume 1 Issue 6

Print ISSN: 1791-2997
Online ISSN:1791-3004

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APA
Strik, H.M., Buhk, J., Wrede, A., Hoffmann, A.L., Bock, H.C., Christmann, M., & Kaina, B. (2008). Rechallenge with temozolomide with different scheduling is effective in recurrent malignant gliomas. Molecular Medicine Reports, 1, 863-867. https://doi.org/10.3892/mmr_00000042
MLA
Strik, H. M., Buhk, J., Wrede, A., Hoffmann, A. L., Bock, H. C., Christmann, M., Kaina, B."Rechallenge with temozolomide with different scheduling is effective in recurrent malignant gliomas". Molecular Medicine Reports 1.6 (2008): 863-867.
Chicago
Strik, H. M., Buhk, J., Wrede, A., Hoffmann, A. L., Bock, H. C., Christmann, M., Kaina, B."Rechallenge with temozolomide with different scheduling is effective in recurrent malignant gliomas". Molecular Medicine Reports 1, no. 6 (2008): 863-867. https://doi.org/10.3892/mmr_00000042