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PDT for Skin Cancers:
What Do We Know About How to Go?
Oseroff, Allan1,
Shieh, Sherry1, Frawley, Noreen1,
Blumenson, Leslie1, Parsons, John1,
Potter, William1, Graham, Andrew1,
Henderson, Barbara 1 and Dougherty, Thomas1
Roswell Park Cancer Institute, Buffalo NY 142631
Abstract-
The skin is an excellent organ for studying PDT, with a high prevalence
of cancers and ready accessibility for treatment monitoring and follow-ups.
At Roswell Park, we have treated > 2,000 basal cell carcinomas (BCCs)
and in situ squamous carcinomas (Bowens disease) with systemic Photofrin-,
and topical ALA-PDT. We have examined hypotheses generated in preclinical
models, and taken clinical results back to the laboratory. With Photofrin,
we confirmed the hypothesis that because of photobleaching, selectivity
increases with decreasing tissue levels of photosensitizer (PS), and
found that ~ 1 mg/kg Photofrin was the lowest, generally effective dose
for treatment 48 h after drug administration. At this drug level, cutaneous
phototoxicity is quite mild. In the low PS, photobleached limit, outcomes
were independent of light doses > 170 J/cm2 at 150 mW/cm2.
However, we still found photodynamic oxygen depletion during the initial
portion of the irradiations in some lesions. With topical ALA-PDT we
examined effects of ALA concentrations, application times and light
doses. For 10-40% ALA, local PS levels were relatively independent of
ALA concentration, and could be 5-10 fold greater than those obtained
with Photofrin. The high PpIX levels make the treatment sensitive to
light dose, particularly at irradiances of 150 mW/cm2. There
was little effect of application time between 4 and 24 h. Given the
high PpIX levels, it is not clear why the outcomes of PDT with ALA are
somewhat inferior to those with Photofrin. We have investigated the
utilities of several potential surrogate metrics to guide therapy. For
ALA-PDT, neither initial PS fluorescence, nor amount of fluorescence
left unbleached after irradiation correlated with outcome, nor did the
extent of damage to the normal skin. However, photobleaching kinetics
appear useful, both in murine models and in patients. The work presented
is supported in part by RO3 CA86850, RO1 CA42278 and PO1 CA55791.
Keywords: pdt,
basal cell carcinoma, photofrin, ala
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