Palifermin (Kepivance, Amgen) is a human recombinant keratinocyte growth factor (KGF) produced in Escherichia coli. When patients with blood cancers undergo high dose chemotherapy and radiation to undergo bone marrow transplant, they usually get severe oral mucositis. Palifermin binds to epithelial cell-surface receptors and stimulates epithelial cell proliferation, differentiation, and upregulation of cytoprotective mechanisms. It reduces the incidence and duration of severe oral mucitis by protecting those cells and stimulating the growth of new epithelial cells to build up the mucosal barrier. This is its structure: C721H1142N202O204S9 .
How does it work?
Palifermin binds specifically to a tyrosine kinase receptor fibroblast growth factor receptor (FGFR2b), which is uniquely expressed in epithelial cells in a variety of tissues.
Animal studies have shown that it enhances the regenerative capacity of epithelial tissues and it prevents oral and intestinal mucositis induced by radio or chemiotherapy.
> It is used to prevent and to treat oral mucositis (and mucositis in general). Studies showed that dose pre-radiotherapy and dose-post are both effective in reducing the duration of severe oral mucositis and its sequelae.
1. BIOLOGICAL EFFECTS:
- Up-regulation of detoxifying enzymes such as nonselenium glutathione peroxidise and gluthatione-S-transferase that protect against ROS. This may be mediated via up-regulation of the transcription factors, which mediate the cellular response to stress via the antioxidant response element.
- Prevention of DNA strand breaks, possibly via up-regulation of DNA polymerases, protein kinase C and tyrosine kinase.
- Inhibition of epithelial cell apoptosis, maybe via modulation of apoptotis and antiapoptotic factors such as Bcl-2, Bax, p53, Akt.
2. MODULATION OF CYTOKINE PROFILE:
- Down-regulation of the Th1 pro-inflammatory cytokines TNF-alfa and INF-gamma
- Up-regulation of the Th2 cytokines IL-4, IL-13
3. REGENERATIVE EFFECTS:
- Reduction of atrophy and ulcer formation and accelerated regrowth in the epithelium
- Enhanced migration, spreading, proliferation and differentiation of epithelial cells with an increase in stem cells.
- Inhibition of desquamation via increased cell-cell adhesion
- An increased number and size of keratohyalin granules in the cells of suprabasal layers
- Stimulation of the EGF receptor, via increased TGF-alfa secretion
- Up-regulation of proteases that are active in tissue remodelling
Palifermin reduces both the incidence and median duration of severe oral mucositis, from 98% to 63% of patients and from 9.0 to 6.0 days.
Patient-reported mouth and throat soreness was also significantly reduced, resulting in improved scores for daily activities such as swallowing, eating, talking and sleeping, and for physical and functional well-being.
Palifermin appears to be well tolerated at the dosages studied
- For patients receiving treatment for solid tumors;
- For patients with hematologic malignancies receiving chemotherapy requiring hematopoietic stem cell transplantation support
More about Palifermin
The effect of palifermin on chemotherapyand radiation therapy-induced mucositis: a review of the current literature
Use of palifermin for the prevention of high-dose methotrexate-induced oral mucositis
Palifermin in the preventive treatment of oral mucositis in autograft patients: data on efficacy and tolerance following marketing approval
The influence of palifermin (Kepivance) on oral mucositis and acute graft versus host disease in patients with hematological diseases undergoing hematopoietic stem cell transplant