J Clin Oncol. 2011 Jun 27. [Epub ahead of print]
Temozolomide in Elderly Patients With Newly Diagnosed Glioblastoma and Poor Performance Status: An ANOCEF Phase II Trial.
Pérez-Lar raya JG, Ducray F, Chinot O, Catry-Thomas I, Taillandier L, Guillamo JS, Campello C, Monjour A, Cartalat-Carel S, Barrie M, Huchet A, Beauchesne P, Matta M, Mokhtari K, Tanguy ML, Honnorat J, Delattre JY.
Jaime Gállego Pérez-Larraya, Karima Mokhtari, Marie-Laure Tanguy, and Jean-Yves Delattre, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moëlle épinière, Unité Mixte de Recherche (UMR) S975, Institut National de la Santé et de la Recherche Médicale (INSERM) U975, Centre National de la Recherche Scientifique, UMR7225, Paris; François Ducray, Stéphanie Cartalat-Carel, and Jérôme Honnorat, Hospices Civils de Lyon, Hôpital Neurologique, Bron; and Université Lyon 1, UMR-S842 and INSERM U842 Lyon, Lyon; Olivier Chinot, Maryline Barrie, and Mona Matta, Assistance Publique-Hôpitaux de Marseille, Centre Hospitalier Universitaire Timone, Université de la Méditerranée, Marseille; Isabelle Catry-Thomas and Aymeri Huchet, Centre Hospitalier Universitaire de Bordeaux, Hôpital Saint André, Bordeaux; Luc Taillandier and Patrick Beauchesne, Centre Hospitalier Universitaire de Nancy, Hôpital Central, Nancy; Jean-Sébastien Guillamo, Centre Hospitalier Universitaire de Caen, Hôpital Côte de Nacre, Caen; Chantal Campello, Centre Hospitalier Universitaire de Nîmes, Hôpital Carémeau, Nîmes; Annick Monjour, Hôpitaux Civils de Colmar, Hôpital Pasteur, Colmar, France.
PURPOSE The management of glioblastoma multiforme (GBM) in elderly patients with poor performance status is not well established. A trial evaluating the efficacy and safety of temozolomide alone in this population was undertaken. PATIENTS AND METHODS Patients age 70 years or older with newly diagnosed GBM and postoperative Karnofsky performance score (KPS) less than 70 were eligible for this nonrandomized phase II trial. Treatment consisted of 150 to 200 mg/m(2)/d temozolomide for 5 days every 4 weeks until disease progression. Radiotherapy was not administered. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, quality of life, and cognition. Results Seventy patients (median age, 77 years; median KPS, 60) were enrolled between July 2007 and February 2009. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 13% and 14% of patients, respectively. Median PFS was 16 weeks (95% CI, 10 to 20 weeks), and median OS was 25 weeks (95% CI, 19 to 28 weeks), comparing favorably with a 12- to 16-week OS expected from a purely supportive approach. Twenty-three patients (33%) improved their KPS by 10 or more points, and 18 (26%) became capable of self-care (KPS ≥ 70). Overall quality of life and cognition improved over time before disease progression. In the 31 tumors evaluated for O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation, a methylated status indicated longer PFS (26 v 11 weeks; P = .03) and OS (31 v 19 weeks; P = .03). CONCLUSION Temozolomide has an acceptable tolerance in elderly patients and GBM and KPS less than 70. It is associated with improvement of functional status in 33% of patients and appears to increase survival compared with supportive care alone, especially in patients with methylated MGMT promoter.