Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of Sulfasalazine for the treatment of progressing malignant gliomas in adults

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.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.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.Current Controlled Trials ISRCTN45828668Despite a wealth of preclinical and clinical research, treatment options for malignant gliomas remain scarce, and median survival of patients barely reaches 15 months despite surgery, radiation and chemotherapy [1].Among several recently discovered biochemical anomalies of malignant gliomas, transcription factor NF-kappaB has emerged as a major molecular determinant of tumor progression and treatment resistance [2]. It is constitutively activated in most high-grade gliomas [3-8], where it promotes the expression of various pro-invasion, anti-apoptotic and cell-cycle related genes [7,9,10]. Inactivation of NF-kappaB blocks glioma gr