Enhancement of interstitial photodynamic therapy by mitomycin C and EO9 in a mouse tumour model

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Abstract
The tumoricidal effect of interstitial photodynamic therapy (IPDT) using 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 RIFI tumours, the light dose required for a given regrowth time or for 50% cure was reduced by a factor of 2 compared with IPDT alone. MMC given immediately after illumination did not increase the effects of IPDT, although MMC plus illumination without photosensitizer produced a significant increase in regrowth time compared with MMC or light alone. Combination of IPDT with EO9, given directly before illumination, only marginally increased the tumour regrowth times at non‐toxic doses. These results demonstrate that combining IPDT with MMC greatly improves the tumour response. Factors such as PDT‐induced hypoxia, pH changes, temperature in‐creases and production of toxic reactive oxygen species by both drugs may play a role in the enhanced MMC cvtotoxicity.