Glioblastoma (GB) is the most common primary brain tumor and also has the worst prognosis
with a mean survival time below 1 year and a 5-year survival rate of less than 2%. AF is a
41kilodalton endogenous and essential protein with antisecretory and anti-inflammatory
effects. Endogenous AF activity increases after exposure to bacterial toxins and endogenous
triggers of inflammation. The active amino-terminal portion of AF has been synthesized as a
16 amino acid peptide (AF-16) and has been used in animal experimental studies. Salovum® is a
product based on egg yolk powder B221® and contains high levels of AF. Salovum® is classified
as food for special medicinal purposes (FSMP) by the European Union an din other countries.
Many tumors show elevated interstitial fluid pressure (IFP) compared to the surrounding
tissue due to vascular leakage, providing a barrier for drug uptake in solid tumors, as well
as poor perfusion, resulting in hypoxia and relative resistance to radiochemotherapy.
AF-16 was reported to significantly reduce the IFP in xenotransplanted human glioblastoma by
inhibiting an ionic pump, NKCC1, in the tumor tissue. Both Salovum® and AF-inducing specific
processed cereals (SPC) prolonged survival in the same models. Systemic temozolomide
treatment combined with AF inducing SPC completely blocked tumor growth in GBM xenografts.
Likewise, SPC treatment abrogated 90% of pre-established syngeneic tumors in immune competent
animals.
Intratumoral delivery of AF-16 potentiated the effect of intratumoral temozolomide in an
experimental model of glioblastoma.
Mechanistically, it remains unclear whether AF's effect in tumor models is mediated through
decrease of IFP and/or immunomodulation. Also, an effect on the complement system through
modulation of circulating complement complexes with proteasome units has been proposed.
Salovum® has been administered to patients with various diseases as, inflammatory bowel
disease, Mb Ménière and mastitis and traumatic brain injury without signs of any adverse
effects.
In a completed phase1-2 trial in participants with primary gliobalstoma the add on of Salovum
during concomitant radiochemotherapa was considered safe and feasible.
The current study is aimed at assessing the efficacy of Salovum in a RCT (randomised
controlled trail).