Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03.
OBJECTIVE
To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM).


METHODS
Thirty-one adult patients (median Karnofsky performance score 90; median age, 51 years) accrued in two centers received involved-field radiotherapy (60 Gy in 2-Gy fractions) and chemotherapy with lomustine 100 mg/m2 (day 1) and TMZ 100 mg/m2/d (days 2 to 6) with individual dose adjustments according to hematologic toxicity.


RESULTS
A median of five courses (range, one to six courses) were delivered. WHO grade 4 hematotoxicity was observed in five patients (16%) and one of these patients died as a result of septicemia. Nonhematologic toxicity included one patient with WHO grade 4 drug-induced hepatitis (leading to discontinuation of lomustine and TMZ) and one patient with WHO grade 2 lung fibrosis (leading to discontinuation of lomustine). The progression-free survival (PFS) rate at 6 months was 61.3%. The median PFS was 9 months (95% CI, 5.3 to 11.7 months), the median overall survival time (MST) was 22.6 months (95% CI, 12.5 to not assessable), the 2-year survival rate was 44.7%. O6-methylguanine-DNA methyltransferase (MGMT) gene-promoter methylation in the tumor tissue was associated with longer PFS (P = .014, log-rank test) and MST (P = .037).


CONCLUSIONS
The combination of lomustine, TMZ, and radiotherapy had acceptable toxicity and yielded promising survival data in patients with newly diagnosed GBM. MGMT gene-promoter methylation was a strong predictor of survival.
Herrlinger
Ulrich
U
Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. Ulrich.Herrlinger@ukb.uni-bonn.de
Rieger
Johannes
J
Koch
Dorothee
D
Loeser
Simon
S
Blaschke
Britta
B
Kortmann
Rolf-Dieter
RD
Steinbach
Joachim P
JP
Hundsberger
Thomas
T
Wick
Wolfgang
W
Meyermann
Richard
R
Tan
Ta-Chih
TC
Sommer
Clemens
C
Bamberg
Michael
M
Reifenberger
Guido
G
Weller
Michael
M
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D019175:DNA Methylation; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000532:radiotherapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D011401:Promoter Regions, Genetic; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
D008130:Lomustine; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide