Effect of recombinant human keratinocyte growth factor (rHuKGF, Palifermin) on radiation-induced mouse urinary bladder dysfunction.

Abstract

To determine the effect of Palifermin (rHuKGF) on acute and late radiation effects in mouse urinary bladder. Graded radiation doses were applied on day 0. Single subcutaneous injections of Palifermin (15 mg/kg) were given on day -2 or day +2. Changes in bladder function (i.e., a reduction in bladder volume by >or=50% of the individual preirradiation value) were assessed by cystometry. Early changes in mouse bladder after irradiation occur in two phases. In the first early phase, a single injection of Palifermin on day -2 increased the ED(50) (dose associated with a positive bladder response in 50% of the mice) from 20.0 +/- 3.3 Gy to 27.1 +/- 6.9 Gy (p < .0051). Palifermin given on day +2 was not beneficial. No significant effects of Palifermin were seen in the second early phase. However, Palifermin administration before, but not after, irradiation, also modified late radiation effects, with an ED50 of 22.2 +/- 4.8 Gy compared with 16.2 +/- 4.9 Gy in control animals (p < .0187). Initial early functional changes in the mouse urinary bladder after irradiation as well as late effects can be significantly reduced by a single administration of Palifermin before irradiation.