BACKGROUND: No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas. METHODS: Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI-Spine Tumor modules were collected. RESULTS: The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients. CONCLUSIONS: This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2020.
BACKGROUND: No standard medical treatment exists for adult patients with recurrent ependymoma, and prospective clinical trials in this population have not succeeded because of its rarity and challenges in accruing patients. The Collaborative Ependymoma Research Network conducted a prospective phase II clinical trial of dose-dense temozolomide (TMZ) and lapatinib, targeting the unmethylated O6-methylguanine-DNA methyltransferase (MGMT) promoter status and increased expression of ErbB2 (human epidermal growth factor receptor 2) and ErbB1 (epidermal growth factor receptor) in ependymomas. METHODS:Patients age 18 or older with histologically proven and progressive ependymoma or anaplastic ependymoma were eligible and received dose-dense TMZ and daily lapatinib. The primary outcome measure was median progression-free survival (PFS). Landmark 6- and 12-month PFS and objective response were measured. Serial assessments of symptom burden using the MD Anderson Symptom Inventory Brain Tumor (MDASI-BT)/MDASI-Spine Tumor modules were collected. RESULTS: The 50 patients enrolled had a median age of 43.5 years, median Karnofsky performance status of 90, and a median of 2 prior relapses. Twenty patients had grade III, 16 grade II, and 8 grade I ependymoma. Half had spinal cord tumors; 15 had a supratentorial tumor, 8 infratentorial, and 2 had disseminated disease. Treatment was well tolerated. The median PFS was 7.8 months (95% CI: 5.5,12.2); the 6- and 12-month PFS rates were 55% and 38%, with 2 complete and 6 partial responses. Measures of symptom burden showed reduction in moderate-severe pain and other disease-related symptoms in most patients. CONCLUSIONS: This treatment, with demonstrated clinical activity with objective responses and prolonged disease control associated with disease-related symptom improvements, is an option as a salvage regimen for adult patients with recurrent ependymoma. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2020.
Authors: Terri S Armstrong; Ibrahima Gning; Tito R Mendoza; Elizabeth Vera-Bolanos; Mark R Gilbert; Laurence D Rhines; Jeffrey S Weinberg; Gisela Sanchez-Williams; Victor Levin; Allen W Burton; Charles Cleeland Journal: J Neurosurg Spine Date: 2010-04
Authors: Kristian W Pajtler; Hendrik Witt; Martin Sill; David T W Jones; Volker Hovestadt; Fabian Kratochwil; Khalida Wani; Ruth Tatevossian; Chandanamali Punchihewa; Pascal Johann; Jüri Reimand; Hans-Jörg Warnatz; Marina Ryzhova; Steve Mack; Vijay Ramaswamy; David Capper; Leonille Schweizer; Laura Sieber; Andrea Wittmann; Zhiqin Huang; Peter van Sluis; Richard Volckmann; Jan Koster; Rogier Versteeg; Daniel Fults; Helen Toledano; Smadar Avigad; Lindsey M Hoffman; Andrew M Donson; Nicholas Foreman; Ekkehard Hewer; Karel Zitterbart; Mark Gilbert; Terri S Armstrong; Nalin Gupta; Jeffrey C Allen; Matthias A Karajannis; David Zagzag; Martin Hasselblatt; Andreas E Kulozik; Olaf Witt; V Peter Collins; Katja von Hoff; Stefan Rutkowski; Torsten Pietsch; Gary Bader; Marie-Laure Yaspo; Andreas von Deimling; Peter Lichter; Michael D Taylor; Richard Gilbertson; David W Ellison; Kenneth Aldape; Andrey Korshunov; Marcel Kool; Stefan M Pfister Journal: Cancer Cell Date: 2015-05-11 Impact factor: 31.743
Authors: David W Ellison; Kenneth D Aldape; David Capper; Maryam Fouladi; Mark R Gilbert; Richard J Gilbertson; Cynthia Hawkins; Thomas E Merchant; Kristian Pajtler; Sriram Venneti; David N Louis Journal: Brain Pathol Date: 2020-06-23 Impact factor: 7.611
Authors: A W Tolcher; S L Gerson; L Denis; C Geyer; L A Hammond; A Patnaik; A D Goetz; G Schwartz; T Edwards; L Reyderman; P Statkevich; D L Cutler; E K Rowinsky Journal: Br J Cancer Date: 2003-04-07 Impact factor: 7.640
Authors: Amr H Saleh; Nardin Samuel; Kyle Juraschka; Mohammad H Saleh; Michael D Taylor; Michael G Fehlings Journal: Nat Rev Cancer Date: 2022-01-14 Impact factor: 69.800
Authors: Elisabeth Bumes; Claudia Fellner; Franz A Fellner; Karin Fleischanderl; Martina Häckl; Stefan Lenz; Ralf Linker; Tim Mirus; Peter J Oefner; Christian Paar; Martin Andreas Proescholdt; Markus J Riemenschneider; Katharina Rosengarth; Serge Weis; Christina Wendl; Sibylle Wimmer; Peter Hau; Wolfram Gronwald; Markus Hutterer Journal: Cancers (Basel) Date: 2022-06-02 Impact factor: 6.575
Authors: Julio C Furlan; Jefferson R Wilson; Eric M Massicotte; Arjun Sahgal; Michael G Fehlings Journal: Neuro Oncol Date: 2022-01-05 Impact factor: 13.029
Authors: Mary Jane Lim-Fat; Maria Macdonald; Sarah Lapointe; Seth Andrew Climans; Chantel Cacciotti; Manik Chahal; Sebastien Perreault; Derek S Tsang; Andrew Gao; Stephen Yip; Julia Keith; Julie Bennett; Vijay Ramaswamy; Jay Detsky; Uri Tabori; Sunit Das; Cynthia Hawkins Journal: Front Oncol Date: 2022-09-23 Impact factor: 5.738
Authors: Walter Berger; Johannes Gojo; Daniela Lötsch; Dominik Kirchhofer; Bernhard Englinger; Li Jiang; Konstantin Okonechnikov; Daniel Senfter; Anna Laemmerer; Lisa Gabler; Christine Pirker; Andrew M Donson; Peter Bannauer; Pia Korbel; Carola N Jaunecker; Jens-Martin Hübner; Lisa Mayr; Sibylle Madlener; Maria T Schmook; Gerda Ricken; Kendra Maaß; Michael Grusch; Klaus Holzmann; Bettina Grasl-Kraupp; Sabine Spiegl-Kreinecker; Jennifer Hsu; Christian Dorfer; Karl Rössler; Amedeo A Azizi; Nicholas K Foreman; Andreas Peyrl; Christine Haberler; Thomas Czech; Irene Slavc; Mariella G Filbin; Kristian W Pajtler; Marcel Kool Journal: Acta Neuropathol Date: 2021-05-27 Impact factor: 17.088