Abstract
Photodynamic therapy (PDT) using Photofrin was used in combination with a hypoxic toxin (mitomycin C, MMC) to treat four patients with recurrent skin metastasis of a mammary carcinoma. In preclinical experiments an additive effect was found for the combination of MMC and PDT for treating subcutaneous RIF1 tumours in mice. When interstitial PDT was combined with a low dose of MMC (administered 15 min before illumination), 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 clinical pilot study, a low dose of Photofrin (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 photosensitivity were scored. After 8-12 weeks of treatment, tumour cure could be achieved by administering light doses > or = 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 necrotic 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 back, lasted maximally 3 weeks. Three main conclusions could be drawn from 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 toxins facilitates treatment by permitting lower doses of photosensitiser to be used (thereby reducing skin phototoxicity) or lower light doses (thereby reducing illumination times and allowing the possibility to treat larger tumour areas). (3) Restoration of skin after PDT in previously treated tumour areas (chemotherapy, radiation therapy and surgery) is very low.
Highlights
Previous published results had demonstrated that Photofrinmediated Photodynamic therapy (PDT) was enhanced by MMC given before illumination when high doses of both photosensitiser (10 mg kg-') and MMC (5 mg kg-') were given (Baas et al, 1994)
Tumour regrowth times decreased significantly (P
Figure lb illustrates the results of these calculations. This analysis demonstrated no significant difference in the incidence of desquamation response between PDT alone or in combination with MMC
Summary
All experiments were carried out in accordance with protocols approved by the local animal welfare committee and conformed to national and international laws. C3H/Km female mice (25-30 g) were inoculated with 1 x 105 RIF1 cells on the lower dorsum. Within 14 days most tumours had grown to a size of 5-6 mm diameter and were used for treatment. Tumour response was evaluated by measuring the tumour three times a week with vernier callipers and calculating the time to increase by 2 mm in mean diameter from the time of treatment (regrowth time). Cures were defined as no visible and palpable tumour 90 days after treatment. Cures were excluded from the analysis of mean regrowth times and were analysed separately. A minimum of six mice per dose group were treated
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