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Oral mucositis

Launched or under launch (2013-2015) : Australia, Canada, Dubai, Egypt, Hungary, India, Israel, Lebanon, Malaysia, Middle East, Philippines, Saudi Arabia, South Africa, Tunisia, Vietnam…

ORAL MUCOSITIS

20mL Class I Medical Device for the treatment of Radiotherapy & Chemotherapy-induced Oral Mucositis (Official Indication)

Physiopathology of Oral Mucositis: Oral mucositis is a very common side effect of cancer chemotherapy. The oral mucosa being one of the fastest growing tissues in the body, cytostatic effect of cancer therapies on oral mucosa cells blocks cellular growth and causes mucositis lesions which cannot heal as long as the cancer treatment continues.
>20 proteolytic enzymes (MMPs) are secreted to clean the ulcers but they also destroy the cellular matrix & stop cell growth. Microbial growth starts, circulating chemicals infiltrate the lesions, causing severe irritation & pain, and the patient suffers until anticancer treatment is stopped.

Ideal Treatment Approach:
1. Clean the ulcer of microbial contaminants
2. Remove continuously the toxic infiltrating chemicals to minimize pain & irritation
3. Neutralize the noxious effect of specific Extra-cellular Matrix (ECM)-destroying MMPs (Matrix Metallo-Proteinases) so as to provide an intact cellular matrix for new cell growth.

Supportive Oncology Care Treatment

1st Protease cleaning spray to treat Radiotherapy & Chemotherapy-induced Oral Mucositis

Physiopathology of Oral Mucositis: Oral mucositis is a very common side effect of cancer chemotherapy. The oral mucosa being one of the fastest growing tissues in the body, cytostatic effect of cancer therapies on oral mucosa cells blocks cellular growth and causes mucositis lesions which cannot heal as long as the cancer treatment continues.

Due to a favorable environment, bacteria start growing which further hampers the cell growth & recovery process. Circulating chemical drugs infiltrate into the ulcer and cause severe irritation, inflammation, & further cellular destruction causing excruciating pain.

 

Why mucositis ulcers rarely heal?

Our body tries to repair the damage & heal the ulcer, but cells cannot grow due to the presence of dead cell debris, multiple contaminants & chemicals in the ulcer cavity.  The cytostatic anti-cancer drugs also block cell growth in normal tissues & stop ulcer healing. Secondly, to clean the injury, >10 proteolytic enzymes called Matrix Metalloproteinases (MMPs) to break the proteins (cellular debris) into smaller molecules, facilitate their excretion, & to prepare a clean environment for cell growth. If the ulcer is not healed rapidly, more & more MMPs are produced.

 

Why MMPs stop healing?

MMPs are proteolytic enzymes, they break proteins.

To heal the ulcer, the daughter cells must attach on a cushion, the Extra Cellular Matrix. ECM is specific to each type of cells & is secreted by mother cells before cell division. It contains a specific association of multiple proteins such as collagen, elastin, laminin, hyaluronic acid. Unfortunately, these proteins are also destroyed by MMPs. In the absence of ECM, daughter cells cannot attach, cannot grow & ulcers cannot heal.

 

Currently available treatments:

Ulcer cleaning: None

Specific mucositis MMP inhibitors: Not yet

Antibacterials: Yes, multiple chlorhexidine-containing OTC drugs as mouthwashes (Peridex, Gelclair, Denticare). They only reduce microbial contaminants.

Artificial human mucus or saliva substitutes: as a lubricant: Biotene (GSK), Neutrasal (Valent), Numoisyn, Aquoral, Salivert, XyliMelts. They reduce pain.

Affecting cell growth (only Rx drugs, FDA approved): Yes, Human recombinant keratinocyte growth factor to reduce incidence & duration of mucositis. It stimulates keratinocyte growth. They have no effect on ulcer cleaning, contaminants….yet, cells cannot grow in a contaminated environment.

 

Why current treatments are not effective: Because mucositis treatment requires a triple target treatment to:

(1) keep the injury free of contaminants,

(2) remove infiltrating chemicals from ulcers to stop irritation & pain, &

(3) allow cell growth by protecting the Extra Cellular Matrix (ECM) from being destroyed by MMPs.

All currently available treatments are mono-target, there is no method to remove chemicals & MMPs continuously from the ulcer & thus block the destruction of ECM by MMPs.

 

VITROBIO APPROACH:

In 1994, the scientists of VITROBIO discovered and patented a hypertonic viscous liquid (VB-Gy), 18 times more osmotically active than sea water yet NON-IRRITANT (International patent 1997: PCT/FR99/01340). Applying VB-Gy on an injury instantly attracts less osmotic – hypotonic liquid from the inner parts of the damaged tissue. Being highly osmotic, this liquid flow is so strong that it removes most of the contaminants from the injury instantly.

We added some specific polymers in VB-Gy to render it filmogen: highly stable & resistant to liquid flow (Patent N° PCT/EP2013/061835). This reduces the frequency of application (once every 2-4h).

The product is present as a 20 ml spray. The film protects the ulcer, the liquid outflow keeps the injury clean by removing from the injured ulcer surface almost all the contaminants, the incoming chemicals and the noxious MMPs to prevent destruction of ECM & allow cell growth.

Due to exclusively topical & filmogen mode of action of Orochem, the product is registered as a Medical Device for sales in EU. This product has no interactions with any other treatment, nor any side effects.

 

Clinical Efficacy:

Full article in J Cancer Res & Treatment (1) 4-11, 2013. DOI: 0.12691/jcrt-1-1-2.

Clinical Trial Protocol:

  • 4-week, controlled trial
  • 7-91 age group,
  • Male & Female patients,
  • Oral Mucositis induced by Cancer therapies
  • OROSOL group: n= 48
  • Control (Classical treatments) group: n= 21
  • 4-5 daily applications of OROSOL

Parameters measured:

  • Overall Mucositis Grade
  • Pain
  • Burning Sensation
  • Bacterial or Fungal Infection
  • New Ulcer Formation
  • Eating Difficulty

 

Fig.1 Mean Intensity of Pain & Burning Sensation

 

 

Fig.2 Mean Overall Mucositis Severity Score (Blue) & Capacity to Take a Solid Diet (Red)

 

What about chemotherapy-unrelated oral ulcers? or buccal dryness?

Whether of chemical, aphthous, or traumatic origin (due to braces or dentures), >24h old oral ulcers share a common physiopathology and require similar modes of therapeutic action to treat and heal them. VITROBIO therefore formulated a Filmogen Oral Gel for the healing of oral ulcers unrelated to chemo treatments: APHTARINE. VITROBIO also conceived a buccal spray that can be used for patients suffering from dry mouth (xerostomia) thanks to its long-lasting hydrating properties.

Conclusion: Marked reduction in mucositis grade, burning
sensation, pain, infection, ulcer expansion, & overall mucositis.