Clinical applications of palifermin: amelioration of oral mucositis and other potential indications

Abstract

Mucositis is one of the most significant toxicities in cancer patients undergoing cytotoxic treatment. It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parentral nutrition, suboptimal delivery of anti-neoplastic treatment, and morbidity and mortality. Palifermin, a recombinant derivative of human keratinocyte growth factor, is the first active agent approved by the FDA for the prevention of severe oral mucositis in patients undergoing haematopoietic stem cell transplantation (HSCT). Several studies have also shown significant reduction in the incidence, severity and/or duration of oral mucositis in other high-risk settings such as concurrent chemoradiotherapy (CT/RT) for patients with head and neck cancer, and use of mucotoxic chemotherapeutic agents such as doxorubicin in sarcoma and fluorouracil for the treatment of colorectal cancer. The reduction in mucositis has translated into amelioration of symptoms and improvement in daily functioning as measured by patient-reported outcome in multiple studies. The clinical response to palifermin appears to be related in part to epithelial proliferation and mucosal thickening. Palifermin also has other potential clinical applications including the acceleration of immune reconstitution and inhibition of graft-versus-host disease in patients undergoing HSCT, and mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT. Palifermin is generally well tolerated with mild-to-moderate skin and oral adverse events. Future studies may expand the use of palifermin into other areas that would benefit from its cytoprotective and regenerative effects.

Prevalence of oral mucositis, dry mouth, and dysphagia in advanced cancer patients

“…Dry mouth and dysphagia showed a similar trend (persistency and worsening), without showing any improvement after admission to a palliative care unit [17]. The mitigation of dysphagia in lung cancer patients treated with concurrent CT/RT was found after treating mucositis with palifermin [3].…”

“…It can have a negative impact on both quality of life and health economics. Severe oral mucositis can contribute to hospitalization, need for narcotic analgesics, total parenteral nutrition, suboptimal delivery of antineoplastic treatment, and morbidity and mortality [3]. Dysphagia is a swallowing disturbance, due to many neuromuscular conditions and consequence of systemic weakness [4].…”

Lovastatin protects keratinocytes from DNA damage-related pro-apoptotic stress responses stimulated by anticancer therapeutics

“…This causes substantial costs to the health system and, most important, also has a considerable impact on the patient's quality of life. Furthermore, dose reduction might become necessary, which limits the efficacy of the antitumor therapy [5,6]. Although numerous options for therapeutic interventions have been investigated, keratinocyte growth factor-1 (palifermin) is the only effective antimucositis drug, which has been approved by the US Food and Drug Administration (US-FDA) and the European Medicines Agency (EMA) as specific anti-mucositis agent [7].…”

Radioprotective Agents for Radiation Therapy: Future Trends

“…In clinical use to prevent or reduce mucositis after bone marrow transplantation [17,18] ACE inhibitors Captopril Angiotensin II inhibition; suppression of radiation-induced proliferation, NOS synthesis, TGF-β induction Radioprotection in animal studies. Results from clinical trials on prevention of radiation pneumonitis have not been definitive [4,[19][20][21] Inhibitors of apoptosis Entolimod Suppression of apoptosis through activation of NF-κB Entolimod protects against lethal total body irradiation in mice and primates [22,23] ACE: Angiotensin-converting enzyme; ROS: Reactive oxygen species; SOD: Superoxide dismutase.…”