Effect of post-exposure administration of keratinocyte growth factor (Palifermin) on radiation effects in oral mucosa in mice.
Oral mucositis is a severe component of the acute radiation syndrome. The present study was initiated to determine the potential of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) to ameliorate oral mucositis in a mouse model after a single radiation exposure. A 3 x 3 mm(2 )area in the center of the lower tongue surface of C3H/Neu mice was irradiated with graded single doses of 25 kV X-rays. Acute mucosal ulceration was used as the quantal end-point for dose-response analyses. Palifermin was applied at a dose of 15 mg/kg on days 0, 1, 2, 3, 4 or 5. For comparison, three injections of 5 or 15 mg/kg on days 1-3 were administered. The ED(50) (dose at which ulceration is expected in 50% of the animals) for irradiation alone was 11.6 +/- 1.2 Gy. Mean latent time was 9.4 +/- 0.2 days; mean ulcer duration was 2.8 +/- 0.2 days. Single injections of rHuKGF did not result in a significant increase in isoeffective radiation doses at any of the administration days. However, the latent time to ulceration was significantly shortened by 1-2 days in all protocols. Repeated administration of rHuKGF (15 mg/kg) resulted a significant increase in ED50 to 16.8 +/- 4.0 Gy (P = 0.0047); the mean latent time was 4.4 +/- 0.9 days. Three injections of 5 mg/kg of Palifermin on days 1-3 yielded an ED50 of 19.4 +/- 1.7 Gy. In this protocol, mean latent time was 6.6 +/- 0.6 days. In conclusion, Palifermin has a potential to reduce the mucositis burden in patients after a single radiation exposure. Repeated injections are required. For three injections, a negative dose-effect of rHuKGF was observed. The optimum dose, number and timing of the administration require further investigation.
Kiliç
Yasemin
Y
Klinik und Poliklinik für Strahlentherapie und Radioonkologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, Dresden, 01307, Germany.
Rajewski
Katja
K
Dörr
Wolfgang
W
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009061:Mouth Mucosa / Q000528:radiation effects*; D013280:Stomatitis / Q000188:drug therapy
D051523:Fibroblast Growth Factor 7