Publikation

Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03

Wissenschaftlicher Artikel/Review - 20.09.2006

Bereiche
PubMed
DOI

Zitation
Herrlinger U, Reifenberger G, Bamberg M, Sommer C, Tan T, Meyermann R, Wick W, Hundsberger T, Steinbach J, Kortmann R, Blaschke B, Loeser S, Koch D, Rieger J, Weller M. Phase II trial of lomustine plus temozolomide chemotherapy in addition to radiotherapy in newly diagnosed glioblastoma: UKT-03. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2006; 24:4412-7.
Art
Wissenschaftlicher Artikel/Review (Englisch)
Zeitschrift
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2006; 24
Veröffentlichungsdatum
20.09.2006
eISSN (Online)
1527-7755
Seiten
4412-7
Kurzbeschreibung/Zielsetzung

PURPOSE: To evaluate toxicity and efficacy of the combination of lomustine, temozolomide (TMZ) and involved-field radiotherapy in patients with newly diagnosed glioblastoma (GBM). PATIENTS AND 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). CONCLUSION: 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.