RTOG 0525: A randomized phase iii trial comparing standard adjuvant temozolomide (tmz) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (gbm)

Détails

ID Serval
serval:BIB_524D87F502CD
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
RTOG 0525: A randomized phase iii trial comparing standard adjuvant temozolomide (tmz) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (gbm)
Titre de la conférence
2011 SNO 16th Annual Scientific Meeting in Conjunction with the AANS/CNS Section on Tumors
Auteur(s)
Gilbert M.R., Wang M., Aldape K.D., Stupp R., Hegi M., Jaeckle K.A., Armstrong T.S., Wefel J.S., Won M., Blumenthal D.T., Mahajan A., Schultz C.J., Erridge S.C., Brown P.D., Chakravarti A., Curran W.J., Mehta M.P.
Adresse
Orange County, California, November 17-20, 2011
ISBN
1522-8517
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
13
Série
Neuro-Oncology
Pages
51
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
Radiotherapy with concomitant and adjuvant TMZ is the standard of care for newly diagnosed GBM. MGMT methylation status may be an important determinant of treatment response. This trial, conducted by the RTOG, EORTC, and NCCTG, determined if intensified TMZ improves survival (OS) or progression free survival (PFS) in all patients or specific to MGMT status. Eligibility criteria included age . 18 yrs, KPS ≥ 60, and existence of a tissue block with . 1cm2 tumor for prospective MGMT and retrospective molecular analysis. Patients were randomized to Arm 1: standard TMZ (150-200 mg/m2 x 5 d) or Arm 2: dd TMZ (75-100 mg/m2 x 21 d) q 4 wks for 6-12 cycles. Symptom burden, quality of life (QOL), and neurocognition were prospectively and longitudinally assessed in a patient subset. 833 patients were randomized (1173 registered). Inadequate tissue (n ¼ 144) was the most frequent reason for nonrandomization.No statistical difference was observed between Arms 1 and 2 for median OS (16.6, 14.9 mo, p ¼ 0.63), median PFS (5.5, 6.7 mo, p ¼ 0.06), or methylation status. MGMT methylation was associated with improved OS (21.2, 14 mo, p , 0.0001), PFS (8.7, 5.7 mo, p , 0.0001), and treatment response (p ¼ 0.012). Cox modeling identifiedMGMT status and RPA class as significant predictors of OS; treatment arm and radiation technique (EORTC vs. RTOG) were not. There was increased grade ≥ 3 toxicity in Arm 2 (19%, 27%, p ¼ 0.008), which was mostly lymphopenia and fatigue. This study did not demonstrate improved efficacy for dd TMZ for newly diagnosed GBM regardless of methylation status. However, it confirmed the prognostic significance of MGMT methylation in GBM, demonstrated the feasibility of tumor tissue collection, molecular stratification, and collection of patient outcomes in a large transatlantic intergroup trial, thereby establishing a viable clinical trial paradigm. Support: NCI U10 CA 21661 and U10 CA37422.
Mots-clé
,
Web of science
Création de la notice
15/12/2011 15:58
Dernière modification de la notice
03/03/2018 17:13
Données d'usage