Long-term survival of patients with glioblastoma treated with radiotherapy
and lomustine plus temozolomide. Glas M, Happold C, Rieger J, Wiewrodt
D, Bähr O, Steinbach JP, Wick W, Kortmann RD, Reifenberger G, Weller M,
Herrlinger U.
J Clin Oncol. 2009 Mar 10;27(8):1257-61.
Division of Clinical Neurooncology, Department of
Neurology, University of Bonn, Sigmund-Freud-Str 25, D-53105 Bonn, Germany.
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/m(2)/d on days 2 to 6;
n = 8 received intensified-dose CCNU 110 mg/m(2) on day 1 and TMZ 150
mg/m(2) 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. O(6)-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.
