Psychiatric side effects of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Remmers (VEGF-R-TKI)

Angiogenesis is a critical factor in the process of growth of a tumor and its
metastases. Angiogenesis is, amongst others, regulated by Vasculo-Endothelial
Growth Factor (VEGF), a family of endogenous compounds. A recently developed
group of anti-cancer drugs, the VEGF-Receptor Tyrosine Kinase Inhibitors
(VEGF-R-TKI) inhibits tumor growth by blocking angiogenesis under the control
of VEGF.
VEGF could play a role in a variety of processes in the central nervous system,
amongst others neuroprotective processes and neurogenesis, the formation of new
neurons, in an interplay of VEGF with other growth factors as Brain Derived
Neurotrophic factor (BDNF) and Fibroblast Growth Factor.
As a consequence, VEGF-R-TKI could interfere with neurogenesis in the
hippocampus. Therefore, one can hypothesize depression as a potental side
effect of VEGF-R-TKI.
Indeed, in clinical practice, VEGF-R-TKI have been linked to psychiatric side
effects. Depression is mentioned as a side effect in the 1B text of the
VEGF-R-TKI sorafenib. Also, delirium has been reported as a side effect. If
these side effects really bear a causal relationship to VEGF-R-TKI, and, if so,
the frequency of psychiatric side effects, in hitherto unknown.

To answer the question, if the use of VEGF-R-TKI is associated with psychiatric
side effects, and if so, to characterzie their symptomatology.

This is a prospective and observational study. In a maximum of 99 oncology
patients who are treated with a VEGF-R-TKI, the treating oncologist during
regular control visits to the outpatient department, inquires about the
presence of side effects. Patients will be aked questions about concentration
difficulties, sadness, loss of interest, irritability, tension or anxiety.
When psychic complaints are present, the severity and relationship with the
VEGF-R-TKI will be assessed and recorded. The psychic symptoms will be graded
as as CTC grade 1 (mild), 2 (moderate), 3 (severe) or 4 (life threatening,
disabling) and the relationship with the VEGF-R-TKI (unlikely, possible,
probable, certain, non classifiable) will be recorded.
Psychiatric referral is mandatory in case of psychic symptoms graded as 3 or 4,
with or without a presumed relationship to the VEGF-R-TKI. In case of grade 1
or 2 symptoms, psychiatric evaluation can be preformed, when the relationship
between these symptoms is considered possible, probable or certain. Judgment
is recorded in the medical chart.
Before treatment with the VEGF-R-TKI, a self-report scale on psychic complaints
(SCL-90) is administered to make comparison possible. In addition, the SCL-90
is administered at 3 and 6 months after the start of therapy.

Minimal burdening of participants. An increase in alertness in treating
oncologists could even lead to improved detection and referral of patients with
psychological distress to psychosocial and psychiatric services. Filling in an
SCL-90 takes 20 minutes at maximum.