Efficacy and tolerability of temozolomide in an alternating weekly regimen in patients with recurrent glioma.
OBJECTIVE
Evaluation of toxicity and efficacy of an alternating weekly regimen of temozolomide administered 1 week on and 1 week off in patients with recurrent glioma.


METHODS
Ninety adult patients with recurrent gliomas accrued in one center received chemotherapy with temozolomide at 150 mg/m(2)/d (days 1 through 7 and 15 through 21 every 4 weeks) with individual dose adjustments according to hematologic toxicity.


RESULTS
A total of 906 treatment weeks were delivered. Grade 4 hematotoxicity according to the Common Terminology Criteria for Adverse Events (CTCAE; version 3.0) was observed in 24 treatment weeks (2.6%). CTCAE grade 4 lymphopenia eventually developed in 11 patients (12%). There were neither cumulative lymphopenias nor opportunistic infections. The progression-free survival (PFS) rate at 6 months for glioblastoma patients was 43.8%. The median PFS in these patients was 24 weeks (95% CI, 17 to 26 weeks), the median survival time from diagnosis of progression was 38 weeks (95% CI, 30 to 46 weeks), and the 1-year survival rate from progression was 23%. O(6)-methylguanine DNA methyltransferase (MGMT) gene promoter methylation in the tumor tissue was not associated with longer PFS (log-rank P = .37).


CONCLUSIONS
These data imply that the alternating weekly schedule is feasible, safe, and effective and clearly warrants investigation in randomized studies. Compared with more protracted low-dose temozolomide schedules, the 1-week-on/1-week-off schedule may be less toxic. We provide preliminary evidence that this dose-dense schedule is also active in patients with tumors lacking MGMT gene promoter methylation.
Department of Neurooncology, University of Heidelberg, Heidelberg, Germany.
Antje
A
Wick
Jörg
J
Felsberg
Joachim P
JP
Steinbach
Ulrich
U
Herrlinger
Michael
M
Platten
Britta
B
Blaschke
Richard
R
Meyermann
Guido
G
Reifenberger
Michael
M
Weller
Wolfgang
W
Wick
D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy*; D019175:DNA Methylation; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D011446:Prospective Studies; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide