Recombinant Epithelial Growth Factor (RhEGF)

Recombinant Epithelial Growth Factor (RhEGF)

PEP Topic 
Mucositis
Description 

Epithelial growth factor (EGF) regulates epithelial cell proliferation, growth, and migration. In addition, it has an effect on angiogenesis for the nutritional support of tissues. Thus, EGF may have an effect on wound healing and tissue generation. Synthesized RehEGF has been studied as an intervention for mucositis.

Effectiveness Not Established

Research Evidence Summaries

Hong, J. P., Lee, S. W., Song, S. Y., Ahn, S. D., Shin, S. S., Choi, E. K., & Kim, J. H. (2009). Recombinant human epidermal growth factor treatment of radiation-induced severe oral mucositis in patients with head and neck malignancies. European Journal of Cancer Care, 18(6), 636-641. doi:10.1111/j.1365-2354.2008.00971.x

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Study Purpose:

Evaluate the wound healing effects of RhEGF in patients with radiation-induced oral mucositis.

Intervention Characteristics/Basic Study Process:

RhEGF 25 mcg/day was applied topically to the oral cavity twice daily for seven days.

Sample Characteristics:

The study was comprised of 11 patients, with an age range of 34-70 years.

Females: 2, Males: 9

Diagnosis Information: Nine patients with head and neck cancer, two patients with lymphoma

Other Key Characteristics: Concurrent chemo/RT five patients. Patients had severe mucositis at the point of study entry.

Setting:

Single site: Seoul, Korea

Study Design:

Prospective trial--pilot study

Measurement Instruments/Methods:

Unaided oral and soft palate evaluation was done on day seven.

Oral mucositis was scored according to RTOG criteria.

Results:

All patients showed improvements in oral mucositis, with decreased mean RTOG grades. Two patients with grade 4 improved to grade 3; two patients with grade 4 improved to grade 2; five patients with grade 3 improved to grade 2; and two patients with grade 3 improved to grade 1. None of the patients had to interrupt RT because of acute mucositis.

Conclusions:

Topical treatment with RhEGF has a therapeutic effect on RT-induced oral mucositis.

Limitations:

Small sample size (pilot study). Mucositis evaluated by unaided eye and restricted or oral and soft palate-may have not been consistent grading if done by different individuals. Sample was too varied, including nasopharyngeal tumors, oropharynx tumors, and hypopharynx tumors and lymphoma. These all differ greatly in the treatment techniques, amount of radiation given, and severity of reaction.

Nursing Implications:

More data are needed to determine effectiveness. Topical applications have limitations as far as adherence to the intended amount of drug and effective coverage of mucosa with medication. Topical application may be easier to apply, but not for everyone, and depending on the taste, an aversion to the taste may occur over time.

Kim, K. I., Kim, J. W., Lee, H. J., Kim, B. S., Bang, S. M., Kim, I., et al. (2013). Recombinant human epidermal growth factor on oral mucositis induced by intensive chemotherapy with stem cell transplantation. American Journal of Hematology, 88(2), 107-112.

doi:10.1002/ajh.23359
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Study Purpose:

Evaluate the effect of topical rhEGF spray for the prevention and treatment of OM in patients receiving intensive chemotherapy followed by HSCT for hematoplogic malignancies.

Intervention Characteristics/Basic Study Process:

Patients were randomly assigned to spray either 50 µg/ml rhEGF or placebo over entire oral mucosa twice daily. Investigators evaluated adherence by examining residual volume of the spray on a daily basis.

Sample Characteristics:

The study was comprised of 58 patients, with a median age of 56.5 years and a range of 18-63.
MALES 53.6%, FEMALES 46.4%
KEY DISEASE CHARACTERISTICS: multiple myeloma, non-Hodgkin lymphoma, ALL, MDS
OTHER KEY SAMPLE CHARACTERISTICS: intensive chemotherapy followed by autologous or allogeneic HSCT

Setting:

SITE: Single site

SETTING TYPE: Inpatient

LOCATION: South Korea

Phase of Care and Clinical Applications:

PHASE OF CARE: Active antitumor treatment

Study Design:

Phase II randomized, double-blind placebo-controlled

Measurement Instruments/Methods:

NCI Common terminology Criteria for Adverse Events (CTCAE), WHO scale, ECOG, modified Oral Mucositis Daily Questionaire  (OMDQ)

Results:

Incidence of NCI grade ≥2 OM 78.6% rhEGF group, 50% in placebo group (p = 0.0496); time to NCI grade 2, 11 days rhEGF; day 10 placebo (p = 0.843), median duration NCI grade ≥2 8.5 days rhEGF and 14.5 days placebo (p = 0.262).


NCI grade ≥3 OM 39.3% in rhEFG group, 32.1% in placebo group (p = 0.577) with median duration eight days rhEGF  versus 16 days placebo group (p = 0.381; QMDQ questionnaire showed reduced limitations in swallowing and drinking in rhEGF group.

Conclusions:

rhEGF did not reduce incidence of NCI grade ≥2 OM. Severe OM with WHO grade ≥3 in rhEGF group had shorter duration of TPN use and opioid analgesic use.

Limitations:

Small sample (<100)

Nursing Implications:

OM is debilitating for patients receiving intensive chemotherapy for hematologic malignancies and can lead to resource intensive episodes. To date, IV palifermin is the only available treatment modality for prevention or treatment of OM. Further research is needed to identify other modalities and to continue to explore the effects of rhEGF on prevention and treatment of chemotherapy-induced OM.

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.

doi:10.1002/cncr.24414
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Study Purpose:

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

Intervention Characteristics/Basic Study Process:

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 Characteristics:

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.

Setting:

Multisite Korea

Study Design:

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

Measurement Instruments/Methods:

RTOG grading

Results:

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.

Conclusions:

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.

Limitations:

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.

Nursing Implications:

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.

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