Topical Recombinant Human Epidermal Growth Factor for Oral Mucositis Induced by Intensive Chemotherapy with Hematopoietic Stem Cell Transplantation: Final Analysis of a Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial

Abstract

The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for oral mucositis (OM) induced by intensive chemotherapy with hematopoietic stem cell transplantation. In this phase 2 study, patients were randomized to either rhEGF (50 microg/mL) or placebo in a 1:1 ratio. The primary endpoint was incidence of National Cancer Institute (NCI) grade ≥2 OM. A total of 138 patients were enrolled in this study. In the intention-to-treat analysis, rhEGF did not reduce the incidence of NCI grade ≥2 OM (p = 0.717) nor reduce its duration (p = 0.725). Secondary endpoints including the day of onset and duration of NCI grade ≥2 OM, the incidence of NCI grade ≥3 OM and its duration, and patient-reported quality of life were also similar between the two groups. In the per-protocol analysis, however, the duration of opioid analgesic use was shorter in the rhEGF group (p = 0.036), and recipients in the rhEGF group required a lower cumulative dose of opioid analgesics than those in the placebo group (p = 0.046), among patients with NCI grade ≥2 OM. Adverse events were mild and transient. This study found no evidence to suggest that rhEGF oral spray reduces the incidence of OM. However, further studies are needed to investigate the effect of rhEGF on OM-induced pain reduction after intensive chemotherapy.

Prevention and Treatment of Chemotherapy and Radiotherapy Induced Oral Mucositis

“…In the study of Kim with co-authors [12], the efficacy of RhEGF was not proven. Controversial results were obtained possibly because the first [12] study was considered successful if it did not develop into II, III or IV degree of OM, and the next study was considered successful if it [11] did not develop only into III or IV degree of OM.…”

“…In all studies, the oncologic treatment method is described: chemotherapy [2], combined chemotherapy and radiotherapy [3,10,11], radiotherapy [11], chemotherapy [12,13,14], combined chemotherapy and radiotherapy [15,16], radiotherapy [17,18], combined chemotherapy and radiotherapy [18], chemotherapy [19], combined chemotherapy and radiotherapy [20], radiotherapy [20], chemotherapy [21], combined chemotherapy and radiotherapy [22,23], radiotherapy [24], combined chemotherapy and radiotherapy [25], radiotherapy [26], combined chemotherapy and radiotherapy [27], chemotherapy [28]. …”

Healing kinetics of oral soft tissue wounds treated with recombinant epidermal growth factor: Translation from a canine model

“…A total of fourteen dogs were employed to discriminate the dose‐dependent effect of rhEGF on oral wound repair. Considering the paucity of the data for the oral mucosa (Kim et al., ), three concentrations were selected in accordance with the literature addressing the treatment of skin wounds in humans (Brown et al., ; Fernández‐Montequín et al., ; Martí‐Carvajal et al., ; Wang, Ma, & Chai, ) or animals (Gainza et al., ; Hong et al., ) with rhEGF. Then, rhEGF incorporated in an ointment vehicle was tested in a discriminating pre‐clinical model.…”

An Investigation into the Prevalence and Treatment of Oral Mucositis After Cancer Treatment

“…Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies (50) rhEGF has been shown to enhance the mucosal wound healing process and has a therapeutic effect on radiation-induced oral mucositis.…”