The therapeutic effect of recombinant human epidermal growth factor (rhEGF) on mucositis in patients with head and neck cancer undergoing radiotherapy with or without chemotherapy: a double-blind placebo-controlled prospective phase II multi-institutional study

Abstract

6021 Background: To evaluate the effectiveness of topically applied human recombinant epidermal growth factor (rhEGF) in the reduction of oral mucositis induced by radiotherapy (or concurrent chemoradiotherapy) in patients with head and neck cancer. Methods: Patients with head and neck cancer receiving external radiotherapy (RT) to the oral cavity or soft palate with conventional fractionation (2 Gy/fraction, 5 fractions weekly, minimum 25 fractions) were entered into a study. Patients were assigned to a placebo group or to one of three EGF-treatment groups (10 μg/ml, 50 μg/ml, or 100 μg/ml). EGF was delivered in a spray twice daily to the whole oral cavity, beginning at the start of RT and continuing through 5 weeks of RT. The primary endpoint examined was mucositis, and the grade of mucositis was evaluated weekly by physicians using the Radiation Therapy Oncology Group (RTOG) scale for acute mucosal morbidity. Responders to EGF were defined as having a RTOG grade 1 score or lower during RT through week 4–5 and don't maintain RTOG grade 2 for week 4–5. Secondary endpoints were WHO oral toxicity scale grade, patient weight, pain score, opioid analgesia use, and time to develop mucositis. Results: Of the 113 patients from six institutions enrolled, 28 were placed in the placebo group, 29 received EGF at 10 μg/ml, 29 at 50 μg/ml, and 27 at 100 μg/ml. Thirteen patients (11.5%) were excluded from further analysis. Forty had nasopharyngeal carcinomas, and 37 had cancers of the oropharynx, 23 of the oral cavity, and 23 in other locations. Compared to placebo, EGF significantly reduced the incidence of severe oral mucositis for the primary endpoint (63% response with EGF at 50 μg/ml vs. 34% response in the control group; p = 0.0227). However, no differences in any secondary endpoints were found between groups. Conclusions: RhEGF oral spray during radiotherapy (or concurrent chemoradiotherapy) is safe and has therapeutic activity against oral mucositis in patients with head and neck cancer. Further phase III study is needed to confirm these results. No significant financial relationships to disclose.