CIPN in Adjuvant Breast Cancer Patients Clinical Trial
Official title:
An Observational STudy to Evaluate the EFfectiveness of OnLife® in Improving Chemotherapy-induced peripherAl NeurOpathy in Patients With Colon or Breast Cancer After End of Adjuvant Therapy
The objective of this observational study is to evaluate the effectiveness of the dietary supplementation "OnLife" in improving signs and symptoms of chemotherapy-induced peripheral neuropathy (CIPN) in adult patients who have finished adjuvant oxaliplatin-containing regimen (colon cancer) or adjuvant paclitaxel regimen (breast cancer). Furthermore, patient-reported outcomes (PROs) and concomitant medication used for the treatment of neuropathic pain will be assessed.
CIPN is a common side effect of many chemotherapeutic agents and often results in dose
limitation, switch to less efficacious agents or even therapy discontinuation. CIPN mainly
affects sensory nerves, while motor or autonomic nerve injury is rare. Therefore, most
patients with CIPN experience numbness, tingling, hyperesthesia, loss of vibratory
perception, and burning pain. Due to the vulnerability of the long nerves, CIPN typically
appears in a 'stocking and glove' distribution.
Chemotherapeutic agents that cause CIPN include platinum compounds (e.g., cisplatin,
oxaliplatin), antitubulins (vinca alkaloids (e.g., vincristine) and taxanes (e.g., docetaxel,
paclitaxel)), proteasome inhibitors (e.g., bortezomib) and immunomodulatory drugs (e.g.,
lenalidomide).
Platinum compounds are known to accumulate in the dorsal root ganglion (DRG) leading to cell
death in sensory neurons. DRG death may account for chronic sensory neuropathy, which
manifests primarily as sensory paresthesias, dysesthesias and sensory ataxia most often
located in the extremities and persists between cycles. In addition, Oxaliplatin directly
regulates the gating of axonal voltage-gated sodium channels, inducing an acute neurotoxicity
which is characterized by peripheral nerve hyperexcitability. Symptoms, like sensitivities to
touching cold items, discomfort swallowing cold liquids, throat discomfort, and muscle
cramps, occur during or shortly after the infusion.
Taxanes are known to cause disruption of microtubule function and therefore microtubule-based
axonal transport. In addition, they interfere with macrophage activation in both the DRG and
peripheral nerve, as well as microglial activation within the spinal cord. These effects
result in a distal axonopathy also referred to as the dying-back phenomenon.
The effectiveness of OnLife® in improving CIPN is based on a patented fatty acid group (FAG)
that comprises palmitoylethanolamide (PEA), alpha-linolenic acid, eicosapentaenoic acid
(EPA), docosahexaenoic acid (DHA), linoleic acid, oleic acid, palmitic acid, stearic acid,
arachidic acid and myristic acid.
PEA, one main component of OnLife®, is an endogenous fatty acid amide belonging to the class
of endocannabinoids and has been shown to have anti-inflammatory, antinociceptive,
neuroprotective and anticonvulsant properties. It is synthesized in response to several
inflammatory and painful disorders (e.g., intestinal inflammation and neuropathic pain) in
order to counteract these pathological states. Clinical research revealed that treatment with
exogenous PEA is effective and safe in various neuropathological conditions, including
chronic idiopathic axonal neuropathy, diabetic neuropathy, nerve compression syndromes, as
well as chemotherapy-induced neuropathic pain.
PEA exerts its analgesic and anti-inflammatory functions in the peripheral nervous system
through its action on sensory neurons and on non-neuronal cells involved in inflammation,
such as mast cells and macrophages. It indirectly activates cannabinoid receptor signaling by
inhibiting the hydrolysis of endocannabinoids. This suppresses nociceptive behaviors and
counteracts macrophage and mast cell activation, thereby reducing pain and other inflammatory
symptoms. Another biological target of PEA is the nuclear peroxisome proliferator-activated
receptor (PPAR)-alpha, expressed in various cells implicated in peripheral nociception,
including dorsal DRG neurons and macrophages. Binding of PEA to PPAR-alpha ultimately results
in reduced transcription of pro-inflammatory genes (e.g., TNF-alpha, IL-6, COX-2, iNOS) as
well as repressed activity of pro-inflammatory transcription factors. In addition, there is
some evidence that binding of PEA to PPAR-alpha may modulate excitability of primary sensory
neurons by direct and indirect mechanisms.
The other fatty acids included in OnLife® have also been shown to have anti-inflammatory
properties.
Currently, a study evaluating the efficacy and safety of OnLife® in patients with CIPN is
carried out at the St. Savvas Anticancer Hospital, Athens by Dr. J. Skarlatos. First results
suggest that OnLife® is reducing pain, numbness and tingle and improving heat/cold
sensitivity as assessed by the physician. PRO, using the DN4 (Douleur Neuropathique 4)
questionnaire, revealed a reduction of the score for diagnosing neuropathic pain during
OnLife® application. Moreover, no patient showed a product-related side effect (date on file,
unpublished).
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