Interim Analysis of Randomized Phase II Study of Recombinant Human Epidermal Growth Factor on Oral Mucositis Induced by Intensive Chemotherapy with Stem Cell Transplantation for Hematologic Malignancies

Abstract 905

Oral mucositis (OM) develops in 40–80% of patients undergoing intensive chemotherapy with stem cell transplantation (SCT) which is often debilitating and influences the quality of life (QoL). A novel drug, recombinant human epidermal growth factor (rhEGF), recently demonstrated promising efficacy and minimal toxicity in the prevention of OM in patients with head and neck cancer receiving radiotherapy (Wu HG et al, Cancer 2009). To evaluate the efficacy and safety of rhEGF for prevention and treatment of OM during SCT, a prospective randomized double-blind placebo-controlled phase II study is being performed (ClinicalTrials.gov identifier, NCT00845819). In this report, results of the scheduled interim analysis are presented. Patients for whom the procedure of SCT for hematologic malignancies was planned were eligible for this study. Patients were randomly assigned to either the rhEGF group or the placebo group, at a 1:1 ratio. Patients were instructed to spray either the 50 μg/mL rhEGF or the placebo over their entire oral mucosa twice daily and to swallow the residual. The rhEGF was administered at the start of intensive chemotherapy until the time of their recovery from neutropenia (absolute neutrophil count >1000 /μL for 3 consecutive days) and disappearance of OM. The severity of OM was assessed daily using the World Health Organization (WHO) scale. Patients also completed an Oral Mucositis Daily Questionnaire (OMDQ) to assess patient-reported QoL (Stiff PJ et al, J Clin Oncol 2006). A total of 138 patients are planned to be enrolled in this study. This interim analysis was performed after the acquisition of data on the 58 patients who were enrolled between March 2009 and June 2010. Twenty-nine patients were assigned to each group. Patient median age in the rhEGF group was 56 (range, 18–63) years and 51 (range, 19–65) years in the placebo group. Autologous SCT was performed on 26 patients (89.7%) from each group, and allogeneic SCT, in the rest (10.3%). Baseline characteristics were not significantly different between the 2 groups. The difference in the incidence of grade 3 or 4 OM between the 2 groups was not significant (p=0.283). The duration of OM in patients with grade 3 or 4 OM tended to be shorter, however, in the rhEGF group than in the placebo group (8.0 [range, 2.0–23.0] days vs. 18.5 [range, 2.0–34.0] days; p=0.108). This result is also supported by the significantly shorter duration of medication use in patients with grade 3 or 4 OM in the rhEGF group than in the placebo (28.0 [range, 17.0–44.0] days vs. 39.5 [range, 17.0–61.0] days; p=0.050). The OMDQ analysis using area-under-the-curve calculation (with a lower score for milder limitation) for patients with grade 3 or 4 OM also showed that rhEGF significantly reduced limitations in swallowing (26.0 [range, 8.0–75.0] vs. 51.5 [range, 19.0–92.0]; p=0.039) and drinking (25.0 [range, 7.0–73.5] vs. 55.5 [range, 20.0–86.0]; p=0.042) compared to placebo. The duration of administration of total parenteral nutrition (TPN) was significantly shorter in the rhEGF group than in the placebo group (7.0 [range, 0.0–25.0] days vs. 16.5 [range, 10.0–32.0] days; p=0.012) in patients with grade 3 or 4 OM. A similar result was observed for the duration of opioid analgesics use (6.0 [range, 0.0–25.0] days vs. 17.0 [range, 0.0–48.0] days; p=0.117). In patients with grade 3 or 4 OM, the rhEGF group showed a significantly shorter length of hospitalization than the placebo group (27.0 [range, 18.0–65.0] days vs. 41.5 [range, 27.0–94.0] days; p=0.022). Adverse events between the 2 groups were not statistically significant. The adverse events in the rhEGF group were nausea (n=2, 6.9%), oral pain (n=1, 3.4%), and taste alteration (n=1, 3.4%). No grade 3 or 4 adverse events developed. To summarize, in patients who received SCT for hematologic malignancies, rhEGF tended to reduce the duration of grade 3 or 4 OM and significantly reduced limitations in swallowing and drinking. In addition, rhEGF significantly reduced the duration of TPN use and hospitalization, and tended to reduce the duration of opioid analgesics use. The rhEGF was generally well tolerated with a favorable safety profile. The results of this interim report demonstrate that rhEGF has a role in the treatment of OM induced by intensive chemotherapy with SCT, and improves QoL. This study is still ongoing, and the final results are expected to be available within 2 years.