PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS: Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS: Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION: These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.
PURPOSE: We evaluated the response to Temodal (Schering-Plough Research Institute, Kenilworth, NJ) of patients with newly diagnosed malignant glioma, as well as the predictive value of quantifying tumor DNA mismatch repair activity and O6-alkylguanine-DNA alkyltransferase (AGT). PATIENTS AND METHODS: Thirty-three patients with newly diagnosed glioblastoma multiforme (GBM) and five patients with newly diagnosed anaplastic astrocytoma (AA) were treated with Temodal at a starting dose of 200 mg/m2 daily for 5 consecutive days with repeat dosing every 28 days after the first daily dose. Immunochemistry for the detection of the human DNA mismatch repair proteins MSH2 and MLH1 and the DNA repair protein AGT was performed with monoclonal antibodies and characterized with respect to percent positive staining. RESULTS: Of the 33 patients with GBM, complete responses (CRs) occurred in three patients, partial responses (PRs) occurred in 14 patients, stable disease (SD) was seen in four patients, and 12 patients developed progressive disease (PD). Toxicity included infrequent grades 3 and 4 myelosuppression, constipation, nausea, and headache. Thirty tumors showed greater than 60% cells that stained for MSH2 and MLH1, with three CRs, 12 PRs, three SDs, and 12 PDs. Eight tumors showed 60% or less cells that stained with antibodies to MSH2 and/or MLH1, with 3 PRs, 3 SDs, and 2 PDs. Eleven tumors showed 20% or greater cells that stained with an antibody to AGT, with 1 PR, 2 SDs, and 8 PDs. Twenty-five tumors showed less than 20% cells that stained for AGT, with 3 CRs, 12 PRs, 4 SDs, and 6 PDs. CONCLUSION: These results suggest that Temodal has activity against newly diagnosed GBM and AA and warrants continued evaluation of this agent. Furthermore, pretherapy analysis of tumor DNA mismatch repair and, particularly, AGT protein expression may identify patients in whom tumors are resistant to Temodal.
Authors: Ian F Pollack; Ronald L Hamilton; Robert W Sobol; Marina N Nikiforova; Yuri E Nikiforov; Maureen A Lyons-Weiler; William A LaFramboise; Peter C Burger; Daniel J Brat; Marc K Rosenblum; Floyd H Gilles; Allan J Yates; Tianni Zhou; Kenneth J Cohen; Jonathan L Finlay; Regina I Jakacki Journal: Pediatr Blood Cancer Date: 2010-12-01 Impact factor: 3.167
Authors: Daniel P Cahill; Kymberly K Levine; Rebecca A Betensky; Patrick J Codd; Candice A Romany; Linsey B Reavie; Tracy T Batchelor; P Andrew Futreal; Michael R Stratton; William T Curry; A John Iafrate; David N Louis Journal: Clin Cancer Res Date: 2007-04-01 Impact factor: 12.531
Authors: Wolfgang Wick; Mirjam Hermisson; Rolf D Kortmann; Wilhelm M Küker; Frank Duffner; Johannes Dichgans; Michael Bamberg; Michael Weller Journal: J Neurooncol Date: 2002-09 Impact factor: 4.130
Authors: Marco Hassler; Michael Micksche; Günther Stockhammer; Josef Pichler; Franz Payer; Brigitte Abuja; Robert Deinsberger; Christine Marosi Journal: Wien Klin Wochenschr Date: 2006-05 Impact factor: 1.704
Authors: Terri S Armstrong; Yumei Cao; Michael E Scheurer; Elizabeth Vera-Bolaños; Rochelle Manning; Mehmet F Okcu; Melissa Bondy; Renke Zhou; Mark R Gilbert Journal: Neuro Oncol Date: 2009-12 Impact factor: 12.300
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: Michael Weller; Roger Stupp; Monika E Hegi; Martin van den Bent; Joerg C Tonn; Marc Sanson; Wolfgang Wick; Guido Reifenberger Journal: Neuro Oncol Date: 2012-09 Impact factor: 12.300
Authors: Gaspar J Kitange; Brett L Carlson; Mark A Schroeder; Patrick T Grogan; Jeff D Lamont; Paul A Decker; Wenting Wu; C David James; Jann N Sarkaria Journal: Neuro Oncol Date: 2008-10-24 Impact factor: 12.300