SELECTIVITY OF MESO-TETRA(HYDROXYPHENYL)PORPHYRINS AND CHLORINS AND OF PHOTOFRIN-II IN CAUSING PHOTODAMAGE IN TUMOR, SKIN, MUSCLE AND BLADDER - THE CONCEPT OF COST-BENEFIT IN ANALYZING THE RESULTS

The selectivities of Photofrin II (Ph II) and four new photosensitizers for tumour and normal tissues have been compared by cost-benefit analysis. Mice were given tetra(p-hydroxyphenyl)porphyrin (p-THPP) or tetra(m-hydroxyphenyl)porphyrin (m-THPP) or the corresponding chlorins (p-THPC, m-THPC, respectively) or Ph II. Twenty-four hours later, tumour (PC6) or normal skin, muscle and bladder were illuminated with 10 J cm-2 light from a dye laser at the appropriate wavelengths. Damage indices were (i) depth of tumour necrosis, (ii) oedema measured by increase in weight of skin, muscle and bladder, (iii) extravasation of systemically administered Evans blue into skin and bladder and (iv) muscle necrosis. Dose-response curves were constructed and selectivities compared by determining the level of benefit (depth of tumour necrosis) obtained for specific costs (damage to normal tissue). m-THPC was by far the most selective for tumour compared with normal tissues and Ph II the least. For example, for a cost in oedema that doubled skin weight, the depth of tumour necrosis was 1.1 mm for Ph II, 3 mm for p-THPP, 4.1 mm for m-THPP, 5.6 mm for p-THPC, and 6.3 mm for m-THPC. m-THPC appears to be a promising sensitizer for clinical investigation. The cost-benefit analysis method addresses the problem of comparing different types of damage. It removes from consideration the individual dose-response curves, and relates benefit (damage to tumour) to cost (damage to normal tissue) for a range of photosensitizers. The method is considered to have wide applicability in drug evaluation (where in the more general case the benefit may relate to an improvement which is not damage-mediated). In clinical medicine, the method is seen to offer a useful way of making progress even in those cases where costs and benefits are a matter of judgement rather than quantification. © 1993 Baillière Tindall.