Wu, H. G., Song, S. Y., Kim, Y. S., Oh, Y. T., Lee, C. G., Keum, K. C., . . . Lee, S. W. (2009). Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy, with or without chemotherapy, for head and neck cancer: A double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial. Cancer, 115(16), 3699-3708.

To evaluate the therapeutic effects of RhEGF on mucositis in patients with head and neck cancer receiving RT, with or without chemotherapy

Patients were randomized to 1 of 4 arms, 10, 50, or 100 mcg/mL study drug or placebo. Patients were instructed to spray study drug over the entire oral mucosa and then swallow the residual, twice daily, from the first day through week 5 of RT. Oral intake was restricted for 30 minutes after spraying. All patients gargled with chlorhexidine. No other mucositis treatment was allowed. Pain medication was allowed. Patients were removed from study if RT was interrupted for 3 or more consecutive days. Every week patients mucositis was graded by a radiation oncologist using RTOG scoring criteria. Patients with treatment delay were removed from the study

Sample Size: 100 patients Age Information: 18-77 years Females: 38 Males: 75 Diagnosis Information: head and neck cancer receiving at least 5 weeks of definitive aim RT or postop RT or definitive chemoradiotherapy. Fraction was 2.0 ± 0.25 Gy with 2 dimensional, 3 dimensional or IMRT Other Key Characteristics: exclusions included cytotoxic chemotherapy or RT within 3 weeks of the study or systemic or topical oral corticosteroids within 30 days of the study. Induction chemotherapy or concurrent cisplatin was allowed.

Multisite Korea

Randomized, double-blind, placebo-controlled phase 2. Randomized per institution and concurrent use of chemotherapy.

RTOG grading

RhEGF significantly reduced the incidence of severe oral mucositis at the primary endpoint (64% response with 50 mcg/mL EGF vs 37% response in the control group)(p =.025). Thirteen patients dropped out of the study. Six cases were dropped from the study due to radiotherapy interruption. Response rate ( ratio of patients who did no develop oral mucositis, with < grade 2) were 57.7%, 64% and 59.1% for RhEGF groups. Only the group treated with 50mcg/ml had significantly higher response rate than placebo ( p =.0246). There were no significant differences between groups at week 4-5.

The EGF spray may have potential benefit for oral mucositis in patients undergoing RT for head and neck cancer. Phase 3 studies are ongoing to confirm these results.

It is difficult to standardize the administration of topical medications, also unable to penetrate the deep regions of the throat No intention to treat analysis of those removed from the study Variations if patients oral mucosal status and overall medical condition, only 5 weeks of observation, the dose was self-administered by patients and recorded in their log books, eating habits of Koreans differ from those of Western societies The spray did not effectively reach the pharyngeal mucosa, therefore there was no effect on pharyngeal mucositis. Patients had varying RT doses, some had IMRT and some had concurrent chemotherapy – there was no subgroup analysis based on these differences that could be expected to affect rate and severity of mucositis.

Due to topical spray administration, there is a potential for improper amount of drug to be administered. Phase 3 results should be reviewed if completed.