Effect of gemcitabine on the tolerance of the lung to single-dose irradiation in C3H mice

In an early phase II trial combining gemcitabine (dFdC) and radiotherapy fo r lung carcinomas, severe pulmonary toxicity was observed. In this framewor k, the objective of this study was to investigate the effect of dFdC on the tolerance of the lungs of C3H mice to single-dose irradiation. The thoraxe s of C3H mice were irradiated with a graded single dose of 8 MV photons; dF dC (150 mg/kg) or saline (control animals) was administered i.p, 3 or 48 h prior to irradiation. Lung tolerance was assessed by the LD50 at 7-180 days after irradiation. For irradiation alone, the LD50 reached 14.45 Gy (95% C I 13,33-15.66 Gy), With a 3-h interval between administration of dFdC and i rradiation, the LD50 reached 13.29 (95% CI 12.26-14.44 Gy); the correspondi ng value with a 48h interval reached 13.01 Gy (95% CI 11.92-14.20 Gy), Our data also suggested a possible effect of dFdC on radiation-induced esophage al toxicity. dFdC has a minimal effect on lung tolerance after single-dose irradiation. However, a proper phase I-II trial should be designed before a ny routine use of combined dFdC and radiotherapy in the thoracic region. (C ) 1999 by Radiation Research Society.