Tejpal Gupta1, Riddhijyoti Talukdar1, Sadhana Kannan2, Archya Dasgupta1, Abhishek Chatterjee1, Vijay Patil3. 1. Department of Radiation Oncology, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India. 2. Department of Clinical Research Secretariat, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India. 3. Department of Medical Oncology, ACTREC/TMH, Tata Memorial Centre, Homi Bhabha National Institute (HBNI), Mumbai, India.
Abstract
Background: This study was designed to compare outcomes of extended adjuvant temozolomide (TMZ) vs standard adjuvant TMZ following radiotherapy (RT) plus concurrent TMZ in newly diagnosed glioblastoma. Methods: This systematic review and meta-analysis was carried out in accordance with Cochrane methodology. Only prospective clinical trials randomly assigning adults with newly diagnosed glioblastoma after concurrent RT/TMZ to 6 cycles of adjuvant TMZ (control arm) or extended (>6 cycles) adjuvant TMZ (experimental arm) were eligible. Primary outcome of interest was overall survival, while progression-free survival and toxicity were secondary endpoints. Hazard ratio (HR) for progression and death with corresponding 95% confidence interval (CI) were computed for individual primary study and pooled using random-effects model. Toxicity was defined as proportion of patients with ≥grade 3 hematologic toxicity and expressed as risk ratio (RR) with 95% CI. Any P-value <.05 was considered statistically significant. Results: Systematic literature review identified five randomized controlled trials comparing standard (6 cycles) vs extended (>6 cycles) adjuvant TMZ in newly diagnosed glioblastoma. Outcome data could be extracted from 358 patients from four primary studies. Extended adjuvant TMZ was not associated with statistically significant reduction in the risk of progression (HR = 0.82, 95% CI: 0.61-1.10; P = .18) or death (HR = 0.87, 95% CI:0.60-1.27; P = .48) compared to standard adjuvant TMZ. Grade ≥3 hematologic toxicity though somewhat higher with extended adjuvant TMZ, was not significantly different between the two arms (RR = 2.01, 95% CI: 0.83-4.87; P = .12). Conclusions: There is low-certainty evidence that extended adjuvant TMZ is not associated with significant survival benefit or increased hematologic toxicity in unselected patients with newly diagnosed glioblastoma compared to standard adjuvant TMZ.
Background: This study was designed to compare outcomes of extended adjuvant temozolomide (TMZ) vs standard adjuvant TMZ following radiotherapy (RT) plus concurrent TMZ in newly diagnosed glioblastoma. Methods: This systematic review and meta-analysis was carried out in accordance with Cochrane methodology. Only prospective clinical trials randomly assigning adults with newly diagnosed glioblastoma after concurrent RT/TMZ to 6 cycles of adjuvant TMZ (control arm) or extended (>6 cycles) adjuvant TMZ (experimental arm) were eligible. Primary outcome of interest was overall survival, while progression-free survival and toxicity were secondary endpoints. Hazard ratio (HR) for progression and death with corresponding 95% confidence interval (CI) were computed for individual primary study and pooled using random-effects model. Toxicity was defined as proportion of patients with ≥grade 3 hematologic toxicity and expressed as risk ratio (RR) with 95% CI. Any P-value <.05 was considered statistically significant. Results: Systematic literature review identified five randomized controlled trials comparing standard (6 cycles) vs extended (>6 cycles) adjuvant TMZ in newly diagnosed glioblastoma. Outcome data could be extracted from 358 patients from four primary studies. Extended adjuvant TMZ was not associated with statistically significant reduction in the risk of progression (HR = 0.82, 95% CI: 0.61-1.10; P = .18) or death (HR = 0.87, 95% CI:0.60-1.27; P = .48) compared to standard adjuvant TMZ. Grade ≥3 hematologic toxicity though somewhat higher with extended adjuvant TMZ, was not significantly different between the two arms (RR = 2.01, 95% CI: 0.83-4.87; P = .12). Conclusions: There is low-certainty evidence that extended adjuvant TMZ is not associated with significant survival benefit or increased hematologic toxicity in unselected patients with newly diagnosed glioblastoma compared to standard adjuvant TMZ.
Authors: Monika E Hegi; Els Genbrugge; Thierry Gorlia; Roger Stupp; Mark R Gilbert; Olivier L Chinot; L Burt Nabors; Greg Jones; Wim Van Criekinge; Josef Straub; Michael Weller Journal: Clin Cancer Res Date: 2018-12-04 Impact factor: 12.531
Authors: C Balañá; M A Vaz; D Lopez; R de la Peñas; J M García-Bueno; M J Molina-Garrido; J M Sepúlveda; J M Cano; C Bugés; S M Sanz; J L Arranz; P Perez-Segura; A Rodriguez; J M Martin; M Benavides; M Gil Journal: Clin Transl Oncol Date: 2013-06-21 Impact factor: 3.405
Authors: Monika E Hegi; Annie-Claire Diserens; Thierry Gorlia; Marie-France Hamou; Nicolas de Tribolet; Michael Weller; Johan M Kros; Johannes A Hainfellner; Warren Mason; Luigi Mariani; Jacoline E C Bromberg; Peter Hau; René O Mirimanoff; J Gregory Cairncross; Robert C Janzer; Roger Stupp Journal: N Engl J Med Date: 2005-03-10 Impact factor: 91.245
Authors: Amy Johnston; Nicola Creighton; Jonathon Parkinson; Eng-Siew Koh; Helen Wheeler; Elizabeth Hovey; Michael Rodriguez; David C Currow Journal: Neurooncol Pract Date: 2019-07-06