Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation

Abstract

Oral mucositis (OM) is one of the most common and debilitating complications in patients undergoing intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) oral spray for OM induced by intensive chemotherapy followed by HSCT. Patients were randomly assigned to either the rhEGF group or placebo group. The severity of OM and self-reported quality of life (QOL) were assessed daily. A total of 58 patients were analyzed. Baseline characteristics were similar between the two groups. The incidence of NCI grade 2 OM was higher in the rhEGF group (78.6% vs. 50%, P 5 0.0496). However, the duration of OM in patients with NCI grade 2 tended to be shorter in the rhEGF group (8.5 days vs. 14.5 days, P 5 0.262). The QOL analysis in patients with World Health Organization (WHO) grade 3 OM showed that rhEGF significantly reduced limitations in swallowing (P 5 0.039) and drinking (P 5 0.042). The duration of hospitalization (P 5 0.047), administration of total parenteral nutrition (P 5 0.012), and the usage of opioid analgesics (P 5 0.018) were significantly shorter in the rhEGF group with WHO grade 3 OM. Adverse events were mild and similar between the two groups. In conclusion, this analysis showed that rhEGF did not reduce the incidence of NCI grade 2 OM. However, the patients with WHO grade 3 OM in the rhEGF group showed better results compared to the placebo group for several secondary endpoints. Am. J. Hematol. 88:107-112, 2013. V

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

“…Another possible explanation for the discrepancy in results is the timing of rhEGF administration. As mentioned in our previous interim analysis, it is possible that rhEGF administered during chemotherapy could negatively stimulate the development of OM, because rhEGF can increase mucosal sensitivity to cancer chemotherapy by accelerating buccal mucosal cell division [13]. Similar results were observed in a recent study evaluating the efficacy of palifermin in patients undergoing autologous HSCT with high-dose melphalan conditioning chemotherapy without TBI [21].…”

“…The study design and protocol were described in detail previously [13]. Patients aged 18 years or older with a documented hematological malignancy who were scheduled to receive intensive chemotherapy followed by autologous or allogeneic HSCT were included.…”

“…The significance levels for the interim and final analyses were 0.003 and 0.047, respectively. As initially planned, an interim analysis was performed when 50% of patients were enrolled [13]. This analysis showed that the primary endpoint was not reached.…”

“…A pre-planned interim analysis of the current study indicated that rhEGF was generally well tolerated, and produced better outcomes than placebo in terms of several secondary endpoints [13]. In this study, we present the final analysis of this trial to evaluate the efficacy and safety of rhEGF oral spray for chemotherapy-induced OM.…”

Review of Preclinical Studies on Treatment of Mucositis and Associated Pain

“…A clinical trial evaluated a recombinant human EGF oral spray in 58 patients with oral mucositis induced by intensive chemotherapy followed by stem cell transplant. Patients with mucositis of grade 3 or higher (according to the World Health Organization scale) who were treated with the EGF oral spray had significantly shorter duration of mucositis, reduced limitations in swallowing and drinking, shorter duration of hospital stays, total parenteral nutrition, and opioid usage (Kim et al, 2013).…”