Abstract
Pancreatic cancer kills over 1700 people each year in Australia. In 2000, there were
1908 new cases diagnosed and it remains one of the least treatable malignancies. In
the USA, it was the fourth leading cause of cancer death in 2004, with 31,860 new
cases and 31,270 recorded deaths. Photodynamic therapy (PDT) is a novel,
potentially useful treatment for locally advanced pancreatic cancer with only limited
research and clinical work addressing this until now. PDT induces non-thermal,
cytotoxic and ischaemic injury to a targeted volume of tissue. During PDT, a
photosensitizer is activated by non-thermal light in the presence of oxygen, generating
cytotoxic oxygen species and inducing cellular injury and microvascular occlusion.
The aim of this thesis was to conduct an animal safety study using two second
generation photosensitizers, talaporfin sodium and verteporfin, to assess the risks of
pancreatic PDT by looking at injury to organs adjacent to the pancreas and assessing
recovery from PDT treatment of the pancreas. The Syrian Golden hamster animal
model was used to compare the results of this research to previous work by other
authors.
The study design incorporated a number of additional experiments, including
quantitative tissue fluorescence techniques, plasma level analysis and histopathology
techniques. The methods for the animal safety study were similar to the approach
used in the clinical setting and provided vital data on the likely risks and side effects
of phototherapy in humans.
The first study, looking at talaporfin sodium, found likely risks of duodenal injury,
gastric injury and death with a limited effect on normal pancreas at photosensitizer
doses likely to be employed for pancreatic cancer PDT. The second study, using
verteporfin, found similar results with a more potent effect on the normal pancreas at
studied drug doses. Both agents had short drug-light intervals, ranging from 15
minutes to 2 hours, reducing the need for pre-treatment hospitalization and short
photosensitivity periods of about one to two weeks. Some animals suffered minor
cutaneous photosensitivity injuries. A human pancreatic cancer PDT pilot study is
feasible and the risks and complications should be acceptable.