gms | German Medical Science

Objective: Because the primary treatment of patients with Glioblastoma multiforme (GBM) is the use ofnalkylating drugs (AD), the role of a rechallenge with AD upon recurrence is subject to discussion. In addition, the pivotal role of cytoreductive surgery for GBM, as demonstrated for the primary treatment, has not yet been evaluated for recurrent GBM. We therefore investigated the role of re-resection and intensified alkylating chemotherapy by both local and systemic regimens in a single institution series of patients with radiographic recurrence of GBM, stratified for MGMT-status.

Methods: Since 12-2006, 31 consecutive patients with recurrent GBM under Stupp regimen were included after informed consent was obtained. Patients were subject to re-resection, implantation of carmustin wafers and treatment with temozolomide one week on/ one week off (150 mg/m²/BS), 4 weeks after surgical treatment. Patients were evaluated pre- and postoperatively by the Karnofsky-, Barthel- and the NIH-Score as well as by serial MR-images (all parameters were collected before surgery, <72h after surgery and every 3 months). Toxicity was closely monitored every week. Overall survival (OAS) and progression free survival (PFS) were determined after 3 months (PFS-3). The MGMT-promoter status was determined by methylation-specific PCR.

Results: 89% had a near complete resection with less than 5ml residual tumor volume. Severe toxicity after WHO CTC was observed in 19 patients [Grade 3 (n=13) and 4 (n=6)]. All patients demonstrated a decreased Karnofsky- and NIH-Score immediately postoperatively, which stabilized until disease progression and even improved after 6 months. As yet, the median PFS is 12 weeks and the median OAS 18.9 months. MGMT-promoter status was determined for 27 patients. 6 (22%) patients were MGMT [+], 21 (78%) patients were MGMT [-]. OAS for MGMT [+]/[-] patients was 19.6 months and 17.5 months, respectively.

Conclusions: As yet, there are no data on the prognosis of patients with a recurrent GBM after Stupp. Therefore, the interpretation of our outcome data must be approached with caution. The high percentage of MGMT-patients probably reflects a negative selection bias, due to the consecutive inclusion of recurrent patients in a single centre study. However, the OAS demonstrated in our population compares favourably with the OAS of the MGMT negative subpopulation published by Hegi. Both the toxicity and clinical data support the feasibility of this regimen.