This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer.


OncologySTAT Editorial Team

Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer.

Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic growth factors were permitted; oral anti-inflammatory, antifungal, or antibiotic solutions were not permitted.

Patients initially were randomized to three treatment arms: weekly palifermin 180 µg/kg throughout CRT, weekly palifermin 180 µg/kg for 4 doses followed by weekly placebo through the remainder of CRT, or weekly placebo throughout CRT. However, adverse event monitoring led to a restart of the study after enrollment of the first 17 patients, with subsequently enrolled patients randomized to receive weekly palifermin 120 µg/kg (n = 92) or weekly placebo (n = 94) throughout CRT (for a minimum of 7 weeks); efficacy analyses were based on these 186 patients. The primary endpoint was the incidence of severe oral mucositis (WHO grade 3 or 4). Oral mucosa assessments occurred twice weekly throughout CRT and until resolution of oral mucositis to WHO grade ≤ 2 or week 15, whichever occurred first. Among secondary endpoints were duration of and time to onset of severe oral mucositis, incidence of grade ≥ 2 xerostomia at month 4, and incidence of treatment breaks (≥ 5 missed consecutive radiation fractions; chemotherapy delays or discontinuation). Time to disease progression and overall survival (OS) also were assessed.

Of 186 patients randomized to weekly palifermin 120 µg/kg or placebo, 79 in the palifermin arm (86%) and 82 in the placebo arm (87%) completed all oral evaluations. Patients in the palifermin group received a mean radiation dose of 59.7 Gy in a mean of 43.5 days and a mean cumulative cisplatin dose of 217.1 mg/m2. Patients in the placebo group received a mean radiation dose of 59.8 Gy in a mean of 43.2 days and a mean cumulative cisplatin dose of 206.4 mg/m2. Severe oral mucositis was observed in 47 patients (51%) in the palifermin group and 63 patients (67%) in the placebo group (P = .027). The median duration of severe oral mucositis was 4.5 days in the palifermin group vs 22.0 days in the placebo group (P = .037), and the median time to develop severe oral mucositis was 45 vs 32 days (P = .022), respectively. Incidence of grade ≥ 2 xerostomia at month 4, incidence of treatment breaks, time to disease progression, and OS did not differ significantly between the two groups.

In conclusion, weekly palifermin at a dose of 120 µg/kg was associated with reduced incidence, increased time to development, and decreased duration of severe oral mucositis in patients undergoing postoperative CRT for locally advanced head and neck cancer. However, differences in other efficacy endpoints were not statistically different in patients receiving palifermin. Further study of palifermin in this patient population is needed.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.