Originally published as JCO Early Release 10.1200/JCO.2008.19.2195 on February 2 2009

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Long-Term Survival of Patients With Glioblastoma Treated With Radiotherapy and Lomustine Plus Temozolomide

From the Division of Clinical Neurooncology, Department of Neurology, University of Bonn; Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen; Dr. Senckenbergisches Institut of Neurooncology, University of Frankfurt, Frankfurt am Main; Department of Neurosurgery, University of Mainz; Department of Neurooncology, University of Heidelberg; Department of Radiation Oncology, University of Leipzig; and Department of Neuropathology, Heinrich-Heine-University of Duesseldorf, Germany; and Department of Neurology, University Hospital Zürich, Zürich, Switzerland.

Corresponding author: Ulrich Herrlinger, MD, Division of Clinical Neurooncology, Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, D-53105 Bonn, Germany; e-mail: Ulrich.Herrlinger{at}ukb.uni-bonn.de.

Purpose To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy.

Patients and Methods Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m² on day 1 and TMZ 100 mg/m²/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m² on day 1 and TMZ 150 mg/m² on days 2 to 6) for up to six courses.

Results In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O⁶-methylguanine–DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%).

Conclusion The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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