Palifermin

Palifermin is a prescription drug used to decrease the effects of oral mucositis in people being treated with chemotherapy for blood-related cancers. Oral mucositis occurs when chemotherapy treatment causes a breakdown in the lining of the oral cavity and gastrointestinal tract, leaving the tissue open to ulceration and infection. The Food and Drug Administration approved palifermin in December 2004. Palifermin is marketed as Kepivance by Amgen. Although use of palifermin adds significantly to the drug cost of treating patients, overall costs may be reduced because costs associated with severe oral mucositis, which have been estimated at $43,000 per patient,^[1] are largely avoided by use of the drug.

Scheme of digestive tract. Mucositis is caused by a loss of cells in the gastrointestinal tract and frequently occurs during chemotherapy of cancer. Palifermin helps to restore the lining in the oral cavity (red) and the rest of the gastrointestinal system.Source: Wikimedia Commons.

Uses

Palifermin is used to decrease the effects of oral mucositis when ALL of the following three conditions are met:

• people with blood-related cancers such as leukemia
• people receiving chemotherapy that suppresses blood cell production or damages blood cells
• people requiring blood stem cell support

How Palifermin is Taken

Palifermin is supplied in vials containing 6.25 mg. Doctors administer palifermin intravenously (IV) at a concentration of 60 μg (micrograms) per kg of body weight daily for three consecutive days before and three consecutive days after chemotherapy.

How Palifermin Works

Palifermin is a genetically engineered form of the protein keratinocyte growth factor (KGF). KGF binds to its receptor located on the surface of cells that line many tissues, including the oral cavity. KGF stimulates proliferation of the cells lining the tongue, cheeks, esophagus, stomach, and intestines.

Animal studies have shown that palifermin, like KGF, causes proliferation of cells lining the tongue, cheeks and gastrointestinal tract. This helps to prevent the erosion of these linings, which is the cause of oral mucositis.

How the Body Affects Palifermin

After IV administration, circulating levels of palifermin decline rapidly over the first 30 minutes post-dose. The drug does not accumulate in the body during consecutive dosing. The half-life of palifermin, or the time needed for the concentration in the blood to be reduced by half, is 4.5–6 hours.

Side Effects

The most common side effects associated with palifermin use are the following:

• Edema
• Pain
• Fever
• Mouth/Tongue Thickness or Discoloration
• Joint aches
• Rash
• Itching
• Skin redness
• Altered taste
• Dysesthesia/hyperesthesia/hypoesthesia/paresthesia (distortions in touch perception)
• Elevated pancreatic enzymes

Risks and Precautions

Because palifermin causes certain cells to proliferate,lab studies have shown that the drug enhances the growth of certain tumor cell lines. However, there is no clinical evidence that palifermin causes tumors.

Drug Interactions

Palifermin is not given within 24 hours before, during infusion of, or within 24 hours after administration of chemotherapy that is toxic to the blood.

Research

Palifermin has been shown to reduce both the incidence and duration of severe mucositis as well as mouth and throat soreness.^[2]

The effectiveness of palifermin was compared to that of placebo in 212 patients undergoing chemotherapy and stem cell transplantation for the treatment of blood cancers.^[3] Severe oral mucositis developed in 63% of palifermin-treated patients and 98% of placebo-treated patients. The severe mucositis lasted less than six days in half the patients treated with palifermin; it lasted less than nine days in half the patients receiving placebo. Scores for mouth soreness, which increase with more severe soreness, were 29 and 47 in palifermin-treated and placebo-treated patients, respectively.

References

1. ↑ Elting LS, Cooksley C, Chambers M, Cantor SB, Manzullo E, Rubenstein EB. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer. 2003 Oct 1;98(7):1531-9. Abstract
2. ↑ Center for International Blood and Marrow Transplant Research Web site. Kepivance: A Breakthrough for Oral Mucositis Associated with Myeloablative Hematopoietic Stem Cell Transplantation. PDF
3. ↑ Spielberger R, Stiff P, Bensinger W, et al. Palifermin for oral mucositis after intensive therapy for hematologic cancers. N Engl J Med. 2004 Dec 16;351(25):2590-8. Abstract | Full Text | PDF

External Links

FDA: Patient Information Sheet