Le, Q.T., Kim, H.E., Schneider, C.J., Murakozy, G., Skladowski, K., Reinisch, S., … Henke, M. (2011). Palifermin reduces severe mucositis in definitive chemoradiotherapy of locally advanced head and neck cancer: A randomized, placebo-controlled study. Journal of Clinical Oncology, 29, 2808–2814.

To evaluate the efficacy and safety of palifermin in the reduction of oral mucositis (OM) associated with definitive chemoradiotherapy for locally advanced head and neck cancer (HNC)

• Patients were randomized to receive 180 mcg/kg palifermin or a matching IV placebo (consisting of sterile water, 4% mannitol, 2% sucrose, 10 mmol/L histadine, 0.010% polysorbate-20, pH 6.5, and no preservatives). Palifermin or placebo was administered as a bolus injection over 30–60 seconds in eight weekly doses, starting three days before initiation of radiation therapy (RT) and then once weekly after the week’s last RT treatment.
• Medications for mucositis and mouthwash solutions containing chlorhexidine, hydrogen peroxide, or diphenhydramine were not allowed.
• Hematopoietic growth factors were allowed only to manage severe anemia or myleosuppresion.

• The study reported on 188 patients with a mean age of 55.
• The study arm sample was 84% male and 16% female; the control arm was 85% male and 15% female.
• Patients were newly diagnosed with unresected stage III–IVB squamous cell carcinoma of the oral cavity, oropharynx, nasopharynx, hypopharynx, or larynx: no evidence of a secondary malignancy; and planned RT dose of more than 50 Gy to different subsites of the inspected oral cavity and oropahrynx.

The study was conducted in a multi-institutional setting.

Patients were undergoing the active treatment phase of care.

This was a randomized, placebo-controlled study.

• The World Health Organization (WHO) Oral Toxicity Scale was used for grading OM.
• Investigators were all trained uniformly, and the same investigators were asked to assess individual patients serially.    
• Patients reported mouth and throat soreness (MTS) scores with the Oral Mucositis Weekly Questionnaire-Head and Neck Cancer.
• Researchers recorded duration of severe OM, time to onset of severe OM, incidence of greater than or equal to 2 xerostomia at month 4, average MTS scores, opioid analgesic use, incidence of RT breaks of at least five consecutive fractions, and incidence of chemotherapy delays.

The incidence of severe OM was significantly lower in patients receiving palifermin than those receiving placebo (54% versus 69%). In the palifermin arm, the median time to severe OM was delayed, median duration of severe OM was shortened, and the incidence of xerostomia at grade 2 or more was lower, favoring palifermin; however, the differences were not significant after multiplicity adjustment.

Opioid analgesic use, average mouth and throat soreness scores, and chemoradiotherapy compliance were not significantly different between treatment arms.

Adverse events were similar between arms. The most common study drug related adverse events were rash, flushing, and dysgeusia. After median follow-up of 25.8 months, overall survival and progression-free survival were similar between the treatment arms.

There was no mention as to whether the study was blinded to the researchers.

Oral mucositis is a severe complication of treatment for head and neck cancer, and effective treatment strategies are still needed. Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemotherapy remains unclear. Effective treatment strategies to manage OM associated with high-dose chemoradiotherapy still are needed.