Aktuelle Neurologie 2007; 34 - P763
DOI: 10.1055/s-2007-988032

Rechallenge of malignant gliomas with Temozolomide – can it be effective?

H Strik 1, JH Buhk 1, MA Nitsche 1, A Giese 1, C Bock 1, M Bähr 1
  • 1Göttingen

No standard treatment of recurrent malignant glioma is established. Moreover, it is unclear if rechallenge with Temozolomide is effective. We present here feasibility and first treatment results of a dose dense, individually dose adapted 21-day regimen with Temozolomide for recurrent malignant gliomas.

18 consecutive patients with recurrent malignant gliomas (15 glioblastomas [GBM], 2 anaplastic astrocytomas, 1 anaplastic oligodendroglioma) were treated. The basic data are: median time to first relapse 9.1 months; median Karnofsky Performance Status 60% (9×50+60%; 9×70–100%); median age 51 (32–73) years; gender: 11 males (61%), 7 females (39%). All patients were pretreated with Radiochemotherapy and Temozolomide 200mg/m2 days 1–5/28 in first line. In eight of the 18 patients, therapy was switched without delay from the conventional 5/28-day regimen to the dose-dense schedule: Temozolomide 100mg/m2 day 1 21/28. The dosage was adapted individually, aiming towards total leukocyte counts of approximately 4,000/µL.

Results: The 21/28 days regimen was better tolerated than the 5/28 days schedule in terms of nausea and fatigue. Blood counts decreased continuously, enabling a gradual dose adaptation. The dosage was kept at 100mg/m2 in 10 patients, reduced to 75mg/m2 in 7 and gradually increased to 130mg/m2 in 1 patient. Hematotoxicity was WHO grade 3 in 2 patients and grade 4 in 1 patient without clinical signs. One patient had a pneumonia WHO grade 4 in the terminal stage of the disease several weeks after discontinuation of the chemotherapy. One other patient had a prolonged constipation.

Response after 3 months in 11 GBM patients was: 1 partial and 1 complete remission (18%), 4 stable diseases (36%), 5 progressive diseases (45%). In the 9 glioblastoma patients with an observation period of more than 6 months, the progression free survival at 6 months (PFS 6) was 44%; the median PFS after relapse was 17.4 weeks; median survival after relapse was 33.6 weeks; median overall survival 13.4+ months.

Second-line treatment with dose-dense Temozolomide at 100mg/m2 day 1–21/28 and individual dose adaptation is feasible for recurrent malignant gliomas. Even in this series with relatively unfavourable prognostic criteria, the rate of objective responses and PFS 6 compare well with other series. We conclude that rechallenge with a dose-dense schedule of Temozolomide can be effective. The results will be controlled in a prospective study.