ENHANCEMENT OF PHOTODYNAMIC THERAPY BY MITOMYCIN-C - A PRECLINICAL AND CLINICAL-STUDY

Photodynamic therapy (PDT) using Photofrin was used in combination wit h a hypoxic toxin (mitomycin C, MMC) to treat four patients with recur rent skin metastasis of a mammary carcinoma. In preclinical experiment s an additive effect was found for the combination of MMC and PDT for treating subcutaneous RIF1 rumours in mice. When interstitial PDT was combined with a low dose of MMC (administered 15 min before illuminati on), the Photofrin dose or light dose could be reduced by a factor of 2 in order to obtain equivalent cure rate or growth delay. In the clin ical pilot study, a low dose of Photfrin (0.75 mg kg(-1)) was used for PDT alone (superficial illumination) or combined with low-dose MMC (5 mg m(-2)). Different tumour areas were illuminated with or without a preceding infusion of MMC. Both tumour response and skin photosensitiv ity were scored. After 8-12 weeks of treatment, tumour cure could be a chieved by administering light doses greater than or equal to 150 J cm (-2) for PDT alone and similar effects were obtained when light doses of 75-87.5 J cm(-2) were given after infusion with MMC. In all cases n ecrotic tissue of both tumour and surrounding skin was observed, which lasted for a mean of 5 months (range 2-20 months). Skin phototoxicity , tested by using a standardised illumination of skin patches on the b ack, lasted maximally 3 weeks. Three main conclusions could be drawn f rom these studies: (1) The enhanced effects of the combination of PDT and MMC observed in mouse tumours can be extrapolated to patients with mammary skin metastasis. (2) The combination of PDT and hypoxic toxin s facilitates treatment by permitting lower doses of photosensitiser t o be used (thereby reducing skin phototoxicity) or lower light doses ( thereby reducing illumination limes and allowing the possibility to tr eat larger tumour areas). (3) Restoration of skin after PDT in previou sly treated tumour areas (chemotherapy, radiation therapy and surgery) is very slow.