2. Adding perphenazine to increase effectiveness of standard
glioblastoma chemoirradiation.
Abstract
In the effort to improve treatment effectiveness in glioblastoma, this
short note reviewed collected data on the pathophysiology of
glioblastoma with particular reference to intersections with the
pharmacology of perphenazine. That study identified five areas of
potentially beneficial intersection. Data showed seemingly 5 independent
perphenazine attributes of benefit to glioblastoma treatment - i)
blocking dopamine receptor 2, ii) reducing centrifugal migration of
subventricular zone cells by blocking dopamine receptor 3, iii) blocking
serotonin receptor 7, iv) activation of protein phosphatase 2, and v)
nausea reduction. Perphenazine is fully compatible with current
chemoirradiation protocols and with the commonly used ancillary
medicines used in clinical practice during the course of glioblastoma.
All these attributes argue for a trial of perphenazine’s addition to
current standard treatment with temozolomide and irradiation. The
subventricular zone seeds the brain with mutated cells that become
recurrent glioblastoma after centrifugal migration. The current paper
shows how perphenazine might reduce that contribution. Perphenazine is
an old, generic, cheap, phenothiazine antipsychotic drug that has been
in continuous clinical use worldwide since the 1950’s. Clinical
experience and research data over these decades have shown perphenazine
to be well-tolerated in psychiatric populations, in normals, and in
non-psychiatric, medically ill populations for whom perphenazine is used
to reduce nausea. For now (Summer, 2020) the nature of glioblastoma
requires a polypharmacy approach until/unless a core feature and means
to address it can be identified in the future. Conclusions: Perphenazine
possesses a remarkable constellation of attributes that recommend its
use in GB treatment.