Henke, M., Alfonsi, M., Foa, P., Giralt, J., Bardet, E., Cerezo, L., … Berger, D. (2011). Palifermin decreases severe oral mucositis of patients undergoing postoperative radiochemotherapy for head and neck cancer: a randomized, placebo-controlled trial. Journal of Clinical Oncology, 29, 2815–2820.

To determine if palifermin reduces severe oral mucositis (OM), defined as grade 3 or 4 on the World Health Organization (WHO) Oral Mucositis Grading Scale, in patients undergoing postoperative radiochemotherapy for locally advanced head and neck cancer

• This study had three arms. In arm 1, patients received 120 ug/kg palifermin per week during radiochemotherapy (at least seven doses). In arm 2, patients received 120 ug/kg palifermin per week for four doses, then placebo throughout the remainder of radiochemotherpy. In arm 3, patients received placebo throughout radiochemotherapy.
• Radiation therapy consisted of conventional or three-dimensional radiation planning for standard fractionation (5 X 2 Gy per week), for a total dose 60 Gy to 66 Gy. Chemotherapy consisted of 100 mg/m² cisplatin on days 1 and 22. Palifermin was administered once, three days prior to starting radiochemotherapy, followed by six once-weekly doses. 
• Local supportive care of normal saline rinses, topical anesthetics, feeding tube, and hematopoietic growth factors were allowed. Anti-inflammatory, antifungal, or antibiotic mouthwash solutions were not permitted.

• The study reported on 186 patients with a mean age of 56.5 years.
• The sample was 82% male and 18% female.
• Patients were resected for pathohistologically documented, high-risk Stage II to IVB squamous cell cancer of the oral cavity, oropharynx, hypopharynx, or larynx and were expected to receive at least 50 Gy to at least two of the main areas of the oral or oropharyngeal mucosa.
• Patients had European Cooperative Oncology Group (ECOG) performance status of 0–2, no history of pancreatitis or acute pancreatitis within the last year, and no prior radiation to the head and neck region or prior to chemotherapy.

This was a multisite study conducted in Australia, Canada, France, Germany, Italy, Spain, and United Kingdom.

Patients were undergoing the active treatment phase of care.

This was a double-blind, randomized, placebo-controlled trial.

• The WHO oral toxicity scale was used.
• Trained evaluators conducted twice weekly assessments (at least 3±1 days apart throughout radiochemotherapy) until resolution of OM to WHO grade 2 or lower or until week 15.
• If OM was not resolved by week 15, weekly assessments were continued until OM reached grade 0 or 1 or until week 24.
• Evaluations immediately analyzed for data quality and accuracy by Clinical Assistance Programs.

• The four-arm palifermin arm was halted because of slow enrollment. Results for the 38 patients on this arm were analyzed separately and matched for the first 38 patients enrolled in the placebo arm.
• Palifermin at 120 ug/kg reduced severe OM in patients with head and neck cancer undergoing concomitant postoperative radiochemotherapy.
• Severe OM was observed in 47 (51%) in the palifermin arm and 63 (67%) in the placebo arm (p = 0.027). The median durations of severe OM were 4.5 days in the palifermin arm and 22.0 days in the placebo arm (p = 0.037). The median times to develop severe OM were 45 or 21 days (p = 0.022) in the palifermin and placeblo arms, respectively.

Palifermin administered prior to initiation of and weekly during concurrent chemotherapy-radiation therapy reduced OM incidence. The study also examined secondary endpoints (i.e., duration and onset, xerostomia, mouth and throat soreness (MTS) score) as well as radiation treatment breaks and chemotherapy delays. Patients receiving palifermin did not experience fewer breaks or lower average MTS  even though these patients did receive fewer opiod analgesics.

This study was supported by Amgen, which manufactures paliferrmin.

Treatment-related OM is debilitating for patients with head and neck cancer undergoing concurrent chemotherapy-radiation therapy. This can significantly impact patient comfort, nutritional status, and response to therapy. Further research is needed to identify effective therapies to better protect the oral mucosa.