ENHANCEMENT OF INTERSTITIAL PHOTODYNAMIC THERAPY BY MITOMYCIN-C AND EO9 IN A MOUSE-TUMOR MODEL

The tumoricidal effect of interstitial photodynamic therapy (IPDT) usi ng Photofrin was found to increase when combined with the bioreductive alkylating agent mitomycin C (MMC) and, to a lesser extent, with the indoloquinone EO9. When MMC was given prior to IPDT of RIF1 tumours, t he light dose required for a given regrowth time or for 50% cure was r educed by a factor of 2 compared with IPDT alone. MMC given immediatel y after illumination did not increase the effects of IPDT, although MM C plus illumination without photosensitizer produced a significant inc rease in regrowth time compared with MCC or light alone. Combination o f IPDT with EO9, given directly before illumination, only marginally i ncreased the tumour regrowth times at non-toxic doses. These results d emonstrate that combining IPDT with MMC greatly improves the tumour re sponse. Factors such as PDT-induced hypoxia, pH changes, temperature i ncreases and production of toxic reactive oxygen species by both drugs may play a role in the enhanced MMC cytotoxicity. (C) 1994 Wiley-Liss , Inc.