Rogowska, Agnieszka Zofia; (2001) Photodynamic therapy for the treatment of cancer of the pancreas. Doctoral thesis (M.D), UCL (University College London).

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Abstract

Cancer of the pancreas is the fifth commonest cause of cancer death and even with treatment, 80-90% of patients die within a year of diagnosis. Photodynamic therapy (PDT) is a non-thermal technique for inducing tissue necrosis. Cytotoxic oxygen species are produced from the interaction between light of a specific wavelength and a photosensitising agent in an oxygenated tissue. Experimental studies using the photosensitisers mTHPC and ALA have shown PDT to have a substantial therapeutic potential for the treatment of pancreatic cancer. mTHPC gave the largest volume of necrosis around treatment sites but clinically causes skin photosensitisation for up to a month. ALA photosensitivity only lasts 1-2 days, but clinical studies show that at the maximum tolerated dose (60mg/kg) the effect is too superficial. The aims of this thesis were: 1. To assess the safety and feasibility of interstitial PDT using mTHPC for the treatment of inoperable pancreatic cancer. To undertake animal studies to investigate a method of enhancing ALA PDT by the addition of the hydroxypyridinone iron chelator, CP94, to slow down the conversion of PPIX (the photoactive derivative of ALA) to haem. The pilot clinical study on 16 patients with localised but inoperable pancreatic cancers (2-6cm in diameter) showed that PDT could produce tumour necrosis with no treatment related mortality and a median survival of 12.5 months. Major complications included bleeding and duodenal stenosis but these were manageable. Experiments on hamsters with cancer transplanted into their pancreas showed significantly higher tissue levels of PPIX and significantly larger volumes of PDT produced tumour necrosis in those given ALA and CP94 compared with ALA alone. This thesis has shown that clinical, interstitial PDT with mTHPC for pancreatic cancer is technically feasible and could produce some survival benefit. This should now be tested in a randomised, controlled trial. The animal experiments showed that adding an iron chelator may enhance ALA PDT. This could now be tested clinically. These encouraging results justify further studies of the possible role of PDT in the management of cancer of the pancreas.

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