BMC Cancer 2009, 9:372 http://www.biomedcentral.com/1471-2407/9/372 PFFigSuarned 3overasll survival of ISRCTN45828668 PFS and overasll survival of ISRCTN45828668. Kaplan- Meier estimates of the PFS and overall survival of the patients from the time of inclusion in ISRCTN45828668. zine is known to induce a release of adenosine from sev- eral cell types [32], and adenosine is a know mitogen for glial cells [33]. Overall, we did not evidence any objective clinical response to sulfasalazine in this study, and on the con- trary, observed some very fast tumor growths despite sul- fasalazine treatment and the occurrence of serious adverse events. The death of two patients during or shortly after sulfasalazine treatment raises significant concerns about the safety of this drug for the treatment of human malig- nant gliomas, even if continued tumor progression in these already debilitated patients (KPS of 40 and 50, respectively) may have contributed to their deaths. In agreement with the independent review committee of the study, these serious adverse events and apparent lack of therapeutic benefit led to the early termination of ISRCTN445828668. Conclusion In conclusion, we strongly oppose the opinion, advocated by several physician and patient support web sites and preclinical reports, that sulfasalazine should be used rou- tinely for the treatment of glioblastoma patients. We also recommend to exert extreme care in the surveillance of gli- oma patients included or to be included in other control- led clinical trials that use this drug. However, the strong preclinical evidence of NF-kappaB in the growth and resistance of malignant gliomas remains unaltered by this study, which only raises questions regarding the value of Sulfasalazine as a clinically useful NF-kappaB inhibitor. We thus encourage the develop- ment of additional clinical trials that target this transcrip- tion factor, using other more specific and/or more potent pharmacological inhibitors of NF-kappaB that are cur- rently being developed (reviewed in [34]). Competing interests The authors declare that they have no competing interests. Authors' contributions PR participated to the design of the study, performed image and data analysis and clinical assessments, and drafted the manuscript, DM participated to the patient recruitment and to the design of the study, MNK partici- pated to image and data collection and analysis, and par- ticipated to the discussion of the manuscript, MA participated to data analysis and discussion of the results, MD performed the histological analyses and NF-kappaB immunostaining, AA participated to the design of the study and, together with SV, performed the statistical analyses and participated to the redaction of the manu- script, SC performed the MGMT methylation assays, MB participated to the analysis of the data, discussion of the results and redaction of the manuscript and VB partici- pated to the design of the study and to the discussion of the results as well as to the redaction of the manuscript. All authors read and approved the final manuscript. Aknowledgements The authors wish to thank Dr F. Collignon and J. Lenelle for participating to the patient recruitment. PAR and MA are respectively a Research Associate a 'Télévie' Research Assistant of the National Fund for Scientific Research of Belgium (FNRS), This work was supported by grants from the Leon Frederic Fund (study sponsor), the Belgian Foun- dation against Cancer, the University Hospital of Liège (FIRS) and the FNRS of Belgium. Additional material Additional file 1 Table S1. inclusion and exclusion criteria of ISRCTN45828668. Click here for file [http://www.biomedcentral.com/content/supplementary/1471- 2407-9-372-S1.PDF] Additional file 2 Table S2 A&B. Characteristics and evolution of patients included in ISRCTN45828668. Click here for file [http://www.biomedcentral.com/content/supplementary/1471- 2407-9-372-S2.PDF] Page 6 of 8 (page number not for citation purposes)