PURPOSE: This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma. PATIENTS AND METHODS: Patients received temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase (MGMT) expression. RESULTS: Twenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (17%). CONCLUSION: This dose-dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.
PURPOSE: This phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma. PATIENTS AND METHODS: Patients received temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase (MGMT) expression. RESULTS: Twenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (17%). CONCLUSION: This dose-dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.
Authors: A K Annamalai; A F Dean; N Kandasamy; K Kovacs; H Burton; D J Halsall; A S Shaw; N M Antoun; H K Cheow; R W Kirollos; J D Pickard; H L Simpson; S J Jefferies; N G Burnet; M Gurnell Journal: Pituitary Date: 2012-09 Impact factor: 4.107
Authors: Michael D Milsom; Moran Jerabek-Willemsen; Chad E Harris; Axel Schambach; Emily Broun; Jeff Bailey; Michael Jansen; David Schleimer; Kalpana Nattamai; Jamie Wilhelm; Amanda Watson; Hartmut Geiger; Geoffrey P Margison; Thomas Moritz; Christopher Baum; Jürgen Thomale; David A Williams Journal: Cancer Res Date: 2008-08-01 Impact factor: 12.701
Authors: Grit Welzel; Julian Gehweiler; Stefanie Brehmer; Jens-Uwe Appelt; Andreas von Deimling; Marcel Seiz-Rosenhagen; Peter Schmiedek; Frederik Wenz; Frank A Giordano Journal: J Neurooncol Date: 2015-06-05 Impact factor: 4.130
Authors: Shadi Lalezari; Arthur P Chou; Anh Tran; Orestes E Solis; Negar Khanlou; Weidong Chen; Sichen Li; Jose A Carrillo; Reshmi Chowdhury; Julia Selfridge; Desiree E Sanchez; Ryan W Wilson; Mira Zurayk; Jonathan Lalezari; Jerry J Lou; Laurel Ormiston; Karen Ancheta; Robert Hanna; Paul Miller; David Piccioni; Benjamin M Ellingson; Colin Buchanan; Paul S Mischel; Phioanh L Nghiemphu; Richard Green; He-Jing Wang; Whitney B Pope; Linda M Liau; Robert M Elashoff; Timothy F Cloughesy; William H Yong; Albert Lai Journal: Neuro Oncol Date: 2013-01-17 Impact factor: 12.300
Authors: Hikmat Assi; Marianela Candolfi; Gregory Baker; Yohei Mineharu; Pedro R Lowenstein; Maria G Castro Journal: Neurosci Lett Date: 2012-08-10 Impact factor: 3.046