Fan, Fung Mei Kathleen; (1998) Application of photodynamic therapy in head and neck oncology. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Photodynamic therapy (PDT) involves the activation of a previously administered photosensitising agent by light resulting in the formation of cytotoxic oxygen species capable of tissue necrosis. The aim of this thesis was to evaluate the role of PDT in the treatment of tumours of the head and neck region both preclinically and clinically. Preclinical studies were carried out on a rabbit model to determine the effect of PDT on normal bone using tumouricidal doses of drug and light. Minimal effects were seen on normal bone using three photosensitisers; Photofrin , aminolaevulinic acid (ALA) and meta tetrahydroxyphenyl chlorin (mTHPC). PDT is an attractive option for the management of nasopharyngeal carcinoma (NPC). Initial pharmacokinetic and PDT studies were carried out on normal rabbits using two photosensitisers, mTHPC and phthalocyanine (AlS2Pc) prior to embarking on clinical therapy. The concern with PDT in the nasopharynx is the close proximity of the brain. Both sensitisers were taken up in the nasopharyngeal mucosa, with no detectable levels in the brain. Using light doses that produced mucosal necrosis in the nasopharynx, no neurological deficit Nor histological damage was observed. Light transmission studies through the skull base confirmed that little light reached the brain from the nasopharynx. The clinical role of PDT was evaluated in patients with oral cancer and dysplasia, using three photosensitisers; Photofrin, ALA and mTHPC. Encouraging results were observed in patients with field cancerization following Photofrin PDT, although the prolonged skin photosensitivity was a major disadvantage. ALA PDT was found to be very effective in superficial epithelial disease (dysplasia). For early invasive disease the best results were seen using mTHPC. Seventeen out of twenty-one T1 and T2 cancers showed complete local responses along with much lower light doses than required for other photosensitisers. With an appropriate choice of photosensitiser, PDT is developing an important role in the management of premalignant and early invasive disease of the mouth.

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