BMC Cancer Research article BioMed Central Open Access Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of Sulfasalazine for the treatment of progressing malignant gliomas in adults Pierre A Robe*1,5,7, Didier H Martin1, Minh T Nguyen-Khac1, Maria Artesi5, Manuel Deprez3, Adelin Albert2, Sophie Vanbelle2, Stephane Califice6, Markus Bredel4 and Vincent Bours5 Address: 1Department of Surgery (Neurosurgery), University of Liège, Domaine du Sart Tilman, B35, 4000 Liège, Belgium, 2Department of Medical Statistics, University of Liège, Domaine du Sart Tilman, B35, 4000 Liège, Belgium, 3Department of Pathology (Neuropathology) University of Liège, Domaine du Sart Tilman, B35, 4000 Liège, Belgium, 4Department of Neurological Surgery, Northwestern Brain Tumor Institute, Northwestern University, 303 E Superior Street, 60611-3015 Chicago, IL, USA, 5Department of Human Genetic - CBIG Research Center, University of Liège, Domaine du Sart Tilman, B35, 4000 Liège, Belgium, 6Oncomethylome Sciences SA, Avenue de l'Hopital 11, 4000 Liège, Belgium and 7Department of Neurosurgery, University of Utrecht Medical Center, Heidelberglaan 100, 3584 CX Utrecht, the Netherlands Email: Pierre A Robe* - p.robe@umcutrecht.nl; Didier H Martin - didier.martin@chu.ulg.ac.be; Minh T Nguyen- Khac - mt.nguyen@student.ulg.ac.be; Maria Artesi - maria.artesi@gmail.com; Manuel Deprez - Manuel.Deprez@ulg.ac.be; Adelin Albert - aalbert@ulg.ac.be; Sophie Vanbelle - sophie.vanbelle@ulg.ac.be; Stephane Califice - stephane.califice@hotmail.com; Markus Bredel - m-bredel@northwestern.edu; Vincent Bours - vbours@ulg.ac.be * Corresponding author Published: 19 October 2009 BMC Cancer 2009, 9:372 doi:10.1186/1471-2407-9-372 This article is available from: http://www.biomedcentral.com/1471-2407/9/372 Received: 24 April 2009 Accepted: 19 October 2009 © 2009 Robe et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract gliomas in adults. Background: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic Methods: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. Results: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. Conclusion: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. Trial Registration: Current Controlled Trials ISRCTN45828668 Page 1 of 8 (page number not for citation purposes)