For patients with progressive or recurrent glioblastoma there is no standard therapy. One strategy is re-exposure to temozolomide in a higher dose. This increase in dosing can be done by 2 regimens. Aim of this study is to compare these 2 dosing regimens concerning toxicity. In study arm A patients receive temozolomide for one week, followed by a week without temozolomide. In study arm B patients receive temozolomide for three weeks, followed by a week without temozolomide. The regimen that is less toxic will be selected for further evaluations.

Inclusion Criteria:

• Progressive or recurrent glioblastoma documented by MRI no earlier than 180 days after first surgery for glioblastoma and no earlier than 90 days after completion of radiotherapy.
• Histological diagnosis of glioblastoma
• Tissue available for the determination of MGMT promoter methylation in the primary tumor or from the recurrent tumor if a patient undergoes a surgical procedure at recurrence prior to study entry.
• Prior treatment with temozolomide administered concomitantly with radiotherapy and at least for two cycles (5/28) as an adjuvant treatment
• Informed consent
• Age 18-80 years
• Karnofsky performance score > 50%
• Neutrophil counts > 1 500/µl
• Platelet counts > 100 000/µl
• Hemoglobin > 10 g/dl
• Serum creatinin < 1.5-fold upper normal range
• ASAT or ALAT < 3-fold upper normal range unless attributed to anticonvulsants
• Alkaline phosphatase < 3-fold upper normal range
• Women with childbearing potential must have a negative serum pregnancy test ≤14 days prior to study enrollment
• Willingness to apply contraception according to local requirements (as stated in patient information)

Exclusion Criteria:

• Progressive or recurrent glioblastoma documented by MRI earlier than 180 days after first surgery for glioblastoma and earlier than 90 days after completion of radiotherapy.
• Treatment with any chemotherapy other than temozolomide according to the schedule of the EORTC NCIC trial (Stupp et al. N Engl J Med 2005;352:987-996) except that an adjuvant starting dose of 200 mg/m2 and more than 6 cycles of adjuvant temozolomide are allowed
• Prior systemic or local treatment with DNA-damaging agents, tyrosine kinase inhibitors or anti-angiogenic agents for any cancer
• Allergy to or other intolerability of temozolomide
• Unable to undergo MRI
• Past medical history of diseases with poor prognosis, e.g. severe coronary heart disease, severe diabetes, immune deficiency, residual deficits after stroke, severe mental retardation
• HIV infection
• Pregnancy
• Breast feeding
• Treatment within in any other clinical trial parallel to the treatment phase of the current study