Chemoradiotherapy of newly diagnosed glioblastoma with intensified temozolomide.
OBJECTIVE
To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma.


METHODS
A total of 41 adult patients (median Karnofsky performance status, 90%; median age, 56 years) were treated with preirradiation TMZ at 150 mg/m(2) (1 week on/1 week off), involved-field radiotherapy combined with concomitant low-dose TMZ (50 mg/m(2)), maintenance TMZ starting at 150 mg/m(2) using a 1-week on/1-week off schedule, plus maintenance indomethacin (25 mg twice daily).


RESULTS
The median follow-up interval was 21.7 months. Grade 4 hematologic toxicity was observed in 15 patients (36.6%). Treatment-related nonhematologic Grade 4-5 toxicity was reported for 2 patients (4.9%). The median progression-free survival was 7.6 months (95% confidence interval, 6.2-10.4). The 1-year survival rate was 73.2% (95% confidence interval, 56.8-84.2%). The presence of O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was associated with significantly superior progression-free survival.


CONCLUSIONS
The dose-dense regimen of TMZ administered in a 1-week on/1-week off schedule resulted in acceptable nonhematologic toxicity. Compared with data from the European Organization for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981-22981/CE.3, patients with an unmethylated MGMT gene promoter appeared not to benefit from intensifying the TMZ schedule regarding the median progression-free survival and overall survival. In contrast, data are promising for patients with a methylated MGMT promoter.
Weiler
Markus
M
Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Hartmann
Christian
C
Wiewrodt
Dorothee
D
Herrlinger
Ulrich
U
Gorlia
Thierry
T
Bähr
Oliver
O
Meyermann
Richard
R
Bamberg
Michael
M
Tatagiba
Marcos
M
von Deimling
Andreas
A
Weller
Michael
M
Wick
Wolfgang
W
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000532:radiotherapy*; D003131:Combined Modality Therapy / Q000379:methods; D016001:Confidence Intervals; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015996:Survival Rate; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D007213:Indomethacin; D000077204:Temozolomide