PURPOSE: Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM. METHODS AND MATERIALS: We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS). RESULTS: Forty-three patients (group 1, n = 21; group 2, n = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients (P < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P = 0.08) despite modest patient numbers. CONCLUSIONS: Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting.
PURPOSE:Temozolomide (TMZ), given concurrently with radiotherapy (RT) and as adjuvant monotherapy afterwards, has led to improved survival in glioblastoma multiforme (GBM). However, it is unclear whether its primary mechanism of action is through enhancement of radiation response, independent cytotoxicity, or both. We sought to determine the relative contribution of concomitant temozolomide in patients treated by concurrent and adjuvant TMZ versus adjuvant TMZ alone in the setting of newly diagnosed GBM. METHODS AND MATERIALS: We identified patients diagnosed with GBM and treated with surgery, involved-field radiotherapy, and chemotherapy at MGH between 2002 and 2004. Eligible patients received either adjuvant temozolomide alone (group 1) or temozolomide concurrently with RT followed by adjuvant TMZ (group 2). The primary endpoint of this retrospective analysis was overall survival (OS). RESULTS: Forty-three patients (group 1, n = 21; group 2, n = 22) were included in this study. The median follow-up was 33.7 months for surviving patients. There were no significant differences in baseline characteristics between these two groups. On univariate analysis, patients who received concurrent and adjuvant temozolomide experienced a 2-year OS of 51% and median survival of 25.5 months, compared with a 2-year OS of 36% and median survival of 15.6 months for group 1 patients (P < 0.05). On multivariable analysis, the hazard ratio (HR) favoring concurrent TMZ trended towards significance (HR = 0.51, P = 0.08) despite modest patient numbers. CONCLUSIONS: Concurrent and adjuvant TMZ was associated with improved survival compared to adjuvant TMZ alone, highlighting the potentiation of radiation effect by temozolomide in the clinical setting.
Authors: J van Rijn; J J Heimans; J van den Berg; P van der Valk; B J Slotman Journal: Int J Radiat Oncol Biol Phys Date: 2000-06-01 Impact factor: 7.038
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Arnab Chakravarti; Michael G Erkkinen; Ulf Nestler; Roger Stupp; Minesh Mehta; Ken Aldape; Mark R Gilbert; Peter McL Black; Jay S Loeffler Journal: Clin Cancer Res Date: 2006-08-01 Impact factor: 12.531
Authors: M Morris; P J Eifel; J Lu; P W Grigsby; C Levenback; R E Stevens; M Rotman; D M Gershenson; D G Mutch Journal: N Engl J Med Date: 1999-04-15 Impact factor: 91.245
Authors: J S Macdonald; S R Smalley; J Benedetti; S A Hundahl; N C Estes; G N Stemmermann; D G Haller; J A Ajani; L L Gunderson; J M Jessup; J A Martenson Journal: N Engl J Med Date: 2001-09-06 Impact factor: 91.245
Authors: R O Dillman; S L Seagren; K J Propert; J Guerra; W L Eaton; M C Perry; R W Carey; E F Frei; M R Green Journal: N Engl J Med Date: 1990-10-04 Impact factor: 91.245
Authors: G Minniti; V Armosini; M Salvati; G Lanzetta; P Caporello; M Mei; M F Osti; R Enrici Maurizi Journal: J Neurooncol Date: 2010-11-05 Impact factor: 4.130
Authors: Christopher A Barker; Maria Chang; Joanne F Chou; Zhigang Zhang; Kathryn Beal; Philip H Gutin; Fabio M Iwamoto Journal: J Neurooncol Date: 2012-06-12 Impact factor: 4.130
Authors: Robert Dubrow; Amy S Darefsky; Daniel I Jacobs; Lesley S Park; Michal G Rose; Maxwell S H Laurans; Joseph T King Journal: Neuro Oncol Date: 2013-09-17 Impact factor: 12.300
Authors: Antonio Silvani; Paola Gaviani; Elena A Lamperti; Marica Eoli; Chiara Falcone; Francesco Dimeco; Ida M Milanesi; Alessandra Erbetta; Amerigo Boiardi; Laura Fariselli; Andrea Salmaggi Journal: J Neurooncol Date: 2009-02-11 Impact factor: 4.130
Authors: Giuseppe Minniti; V De Sanctis; R Muni; D Rasio; G Lanzetta; A Bozzao; M F Osti; M Salvati; M Valeriani; G P Cantore; R Maurizi Enrici Journal: J Neurooncol Date: 2008-08-29 Impact factor: 4.130