Oral mucositis, the breakdown of the mucosal lining of the oropharynx, occurs as a result of a toxic insult to the normal epithelium of the oral mucosa. Typically this is seen after exposure to a toxic agent such as radiation or
chemotherapy; therefore, it is a frequent problem for patients undergoing treatment for
cancer. In clinical trials,
mucositis has been reported in up to 98% of patients receiving high-dose
chemotherapy followed by hematological stem cell transplant. When
mucositis develops it causes severe patient symptoms such as
pain, but it is also associated with inferior clinical outcomes including increased
infection,
narcotic use and even mortality. In clinical trials,
palifermin, a recombinant humanized
keratinocyte growth factor (rHuKGF), has demonstrated an ability to decrease the incidence and duration of
mucositis. In the registrational phase III trial in patients undergoing stem cell transplant for
hematological malignancies, only 63% of patients who received
palifermin developed World Health Organization grade 3 or 4
mucositis compared to 98% of patients on the placebo arm (1). The patients on the
palifermin arm also had a shorter duration of
mucositis with significantly decreased
pain, use of
narcotics, need for
total parenteral nutrition and
febrile neutropenia. Based on these results,
palifermin became the first
drug that has been approved by the U.S. Food and Drug Administration (FDA) to decrease the incidence and duration of severe
oral mucositis in patients with
hematological malignancies receiving high-dose
chemotherapy requiring hematopoietic stem cell support. The development of
mucositis is also a problem for patients receiving treatment for nonhematological
tumors. In clinical trials,
mucositis has been reported in over 75% of patients receiving combined chemo-/
radiotherapy for
head and neck cancer or
fluorouracil for metastatic
colon cancer. Initial phase I and II clinical trials of
palifermin have demonstrated a benefit in patients receiving
chemotherapy with or without
radiation therapy for solid
tumors; however, large phase III trials need to be completed before
palifermin can gain FDA approval for this indication.