Dose-intensity temozolomide after concurrent chemoradiotherapy in operated high-grade gliomas.
OBJECTIVE
We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy.


METHODS
From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30-70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m(2) for the first cycle, 100 mg/m(2) for the second, 125 mg/m(2) for the third, and 150 mg/m(2) from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks.


RESULTS
After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02-14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis).


CONCLUSIONS
The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).
Dall'oglio
Stefano
S
Radiotherapy Department, Ospedale Civile Maggiore, Piazzale A. Stefani 1, 37126 Verona, Italy. stefano.dalloglio@azosp.vr.it
D'Amico
Anna
A
Pioli
Fabio
F
Gabbani
Milena
M
Pasini
Felice
F
Passarin
Maria Grazia
MG
Talacchi
Andrea
A
Turazzi
Sergio
S
Maluta
Sergio
S
D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000145:classification / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000145:classification / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000077204:Temozolomide
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide