Randomized Study of Postoperative Radiotherapy and Simultaneous Temozolomide without Adjuvant Chemotherapy for Glioblastoma

19 November 2008

Kocher M, Frommolt P, Borberg SK, Rühl U, Steingräber M, Niewald M, Staar S, Stuschke M, Becker G, Fischedick AR, Herfarth K, Grauthoff H, Müller RP.

Department of Radiotherapy, University Hospital, Cologne, Germany, martin.kocher@....

PURPOSE: : To evaluate the efficacy of simultaneous postoperative temozolomide radiochemotherapy in glioblastoma patients. PATIENTS AND METHODS: : From February 2002 to July 2004, n = 65 patients from 11 German centers with macroscopic complete tumor resection were randomized to receive either postoperative radiotherapy alone (RT, n = 35) or postoperative radiotherapy with simultaneous temozolomide (RT + TMZ, n = 30). Patients were stratified according to age (</=/>50 years) and WHO performance score (0-1 vs. 2). RT consisted of 60 Gy in 30 fractions. In the RT + TMZ arm, oral TMZ was administered daily at a dose of 75 mg/m(2) including weekends (40-42 doses). Adjuvant treatment was not given, but in both arms, patients with recurrent tumors and in good condition (WHO 0-2) were scheduled for salvage chemotherapy with TMZ. RESULTS: : The trial was stopped early due to the results of EORTC-study 26981-22981 that showed a survival benefit for the combination of concomitant and adjuvant TMZ compared to radiotherapy alone. In total, 62/65 patients were evaluable. Stratification variables were well balanced (</= 50 years 26% vs. 20%, WHO 0-1 91% vs. 100%). Neither overall survival (median 17 vs. 15 months) nor progression-free survival (median 7 vs. 6 months) differed significantly between the two arms. In the RT (RT + TMZ) arm, 76% (62%) of the progressing patients received salvage chemotherapy with TMZ, 36% (50%) had a second resection. There was a time-constant trend for increased general quality of life (EORTC questionnaire QLQ C30) and brain-specific quality of life (EORTC questionnaire B20) in the combined arm. Lymphopenia G3-4 was more frequent (33 vs. 6%) in the RT + TMZ arm. CONCLUSION: : After early closure of this trial, a benefit for progression-free survival for simultaneous TMZ radiochemotherapy alone could not be demonstrated. In both arms, salvage therapies were frequently used and probably had a major effect on overall survival.

PMID: 19016015 [PubMed - as supplied by publisher]

Commento Personale: Questo studio dimostra come l’utilizzo del Temodal combinato alla radioterapia non sia una panacea, offrendo solamente un minimo vantaggio sulla sopravvivenza rispetto alla radioterapia da sola. Il vantaggio nell’utilizzo del Temodal è stato dimostrato solo in coloro i quali presentano l’enzima MGMT metilato. In altri termini occorrerebbe intraprendere strade diverse dal Temodal (ad esempio, l’Avastin o i trattamenti loco regionali come il CerePro o il Novocure TTF o meglio ancora i vaccini negli Stati Uniti come il DCVax e il CDX-110, con l’esclusione del Gliadel) nei nuovi diagnosticati che presentano l’MGMT non metilato. Chiaramente dovrebbero essere i medici ad essere a conoscenza di questi nuovi prodotti della farmaceutica disponibili negli Stati Uniti e ad avvisare i pazienti prima di una craniotomia (dove possibile), per dar loro la possibilità di una scelta di cura migliore. Ma questa è, fondamentalmente, una utopia.

Source Strahlenther Onkol. 2008 Nov;184(11):572-579. Epub 2008 Nov 19