Modification by vasoactive drugs of tumour destruction by photodynamic therapy with haematoporphyrin derivative

Abstract

Since the vascular endothelium is a primary site of damage after photodynamic therapy (PDT), it seemed likely that drugs which affect the vasculature may modify the outcome of PDT. Noradrenaline, propranolol, hydralazine and phenoxybenzamine inhibited photodynamic damage to tumours if these drugs were administered concurrently with HPD, 2 h before irradiation. This inhibition was associated with reduced uptake of HPD into tumours. There was no inhibition if irradiation was delayed until 24 h after administration of vasoactive drug, presumably because HPD uptake continued after the drugs had ceased to affect the vasculature. Verapamil enhanced photodynamic destruction of tumours when administered concurrently with HPD and the enhancement was associated with increased uptake of HPD into tumours. Verapamil neither increased uptake of HPD nor enhanced photodynamic destruction of cells in vitro. When verapamil was administered after irradiation, regrowth of tumours was inhibited. A similar effect was previously demonstrated with glucocorticoids. Other calcium channel blocking agents diltiazem and nifedipine had no effect on uptake of HPD or inhibition of regrowth of tumours after PDT. Inhibition of capillary or stromal ingrowth into tumours seems a plausible explanation of this effect of verapamil. This commonly used drug may be useful to enhance the efficacy of PDT.