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


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.


CONCLUSIONS
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.


BACKGROUND
Current Controlled Trials ISRCTN45828668.
Robe
Pierre A
PA
Department of Surgery (Neurosurgery), University of Liège, Domaine du Sart Tilman, B35, 4000 Liège, Belgium. p.robe@umcutrecht.nl
Martin
Didier H
DH
Nguyen-Khac
Minh T
MT
Artesi
Maria
M
Deprez
Manuel
M
Albert
Adelin
A
Vanbelle
Sophie
S
Califice
Stephane
S
Bredel
Markus
M
Bours
Vincent
V
D000328:Adult; D018450:Disease Progression; D057239:Early Termination of Clinical Trials; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012460:Sulfasalazine / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
D012460:Sulfasalazine