Photodynamic therapy for the treatment of oral cancer
Photodynamic therapy (PDT) describes an interaction of a drug, light and oxygen that results in cell killing. The aim of this thesis is to describe the potential clinical applications of the three most commonly used drugs in PDT - aminolaevulinic acid (ALA), Photofrin and Foscan . Before it was considered safe to use this therapy on patients, a series of preclinical studies were undertaken to establish the safety of the treatment and to try to understand the likely clinical effects on normal tissues. Following this, a series of studies was undertaken to look at the biological effect of PDT on normal and neoplastic tissue. These studies showed the treatment to be safe and effective in destroying tissue while allowing healing with preservation of sufficient tissue structure to maintain tissue contour and function. Next, clinical studies were undertaken on dysplasia, early oral cancer and field change disease using the 3 sensitisers. ALA was found to be useful in the treatment of dysplasia, but has a very superficial effect so is not indicated for treatment of invasive disease. Photofrin and Foscan have a much deeper effect and can be used to treat early cancer and superficial field change disease. Both drugs have problems of prolonged sensitivity to light varying from 2 weeks (Foscan ) to 3 months (Photofrin ). Treatment times also vary from 200s (Foscan ) to 1000s (Photofrin ). The depth of effect limits the use of surface illumination to a maximum of 1cm, however, the use of interstitial therapy, where the light is delivered directly into a neoplastic tissue target allows more advanced cancers to be treated. Currently, Foscan is the only drug licensed for head and neck cancer and then only in the advanced or palliative setting where all other options have been exhausted or are not appropriate. While there is no single drug or technique for the treatment of all stages of oral cancer, PDT is now beginning to be used alongside surgery, radiotherapy and chemotherapy.