Modulation of radiation-induced oral mucositis by thalidomide : Preclinical studies.

Abstract

PURPOSE:

Oral mucositis is a common, dose-limiting early side effect of radio(chemo)therapy for head-and-neck tumors. The epithelial radiation response is accompanied by changes in the inflammatory signaling cascades mediated by the transcription factor nuclear factor-kappa B (NF-κB). The present study was initiated to determine the effect of the NF-κB inhibitor thalidomide on the clinical manifestation of oral mucositis in the established mouse tongue model.

MATERIALS AND METHODS:

Treatment protocols comprised single dose irradiation and daily fractionated irradiation (5  fractions of 3 Gy/week) over 1 (days 0-4) or 2 weeks (days 0-4, 7-11), alone or in combination with daily thalidomide application (100 mg/kg intraperitoneally) over varying time intervals. Fractionation protocols were terminated by graded local radiation doses (day 7/14) to generate full dose-effect curves. Tongue epithelial ulcerations, corresponding to confluent mucositis, served as the clinically relevant endpoint.

RESULTS:

Thalidomide application did not show a significant radioprotective potential when administered in combination with single dose irradiation. Thalidomide in combination with one week of fractionated irradiation significantly increased the isoeffective top-up doses. Similar results were observed during two weeks of fractionated irradiation in all but one experiment.

CONCLUSION:

Thalidomide treatment demonstrated a significant mucositis-ameliorating effect during fractionated irradiation, which is likely to result from NF-κB inhibition. However, further mechanistic studies are required to define the underlying mechanisms of the observed mucoprotective effect.

• Authors: Katharina Frings, Sylvia Gruber, Peter Kuess, Miriam Kleiter, Wolfgang Dörr
• Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] (Strahlenther Onkol) Vol. 192 Issue 8 Pg. 561-8 (Aug 2016) ISSN: 1439-099X [Electronic] Germany
• Vernacular Title: Modulation der strahleninduzierten oralen Mukositis durch Thalidomid : Präklinische Studien.
• PMID: 27282278 (Publication Type: Journal Article)

Chemical References

• Immunosuppressive Agents
• NF-kappa B
• Thalidomide

Topics

• Animals
• Dose-Response Relationship, Drug
• Dose-Response Relationship, Radiation
• Immunosuppressive Agents (administration & dosage)
• Mice
• Mice, Inbred C3H
• Mouth Mucosa (drug effects, pathology, radiation effects)
• NF-kappa B (antagonists & inhibitors)
• Radiation Injuries (drug therapy, pathology)
• Stomatitis (drug therapy, pathology)
• Thalidomide (administration & dosage)
• Treatment Outcome