Photodynamic therapy (PDT) is a method for the treatment of cancer that involves the administration of systemic or topical photosensitizing drugs that are preferentially taken up by the tumour and then activated in the presence of light to cause tissue destruction (Dougherty, 1988). Photodynamic therapy works by the generation of singlet oxygen that results in damage to cell membrane structures, microvascular ischaemia, and tissue necrosis. Numerous clinical trials of photodynamic therapy have been conducted over the past decade and PDT has been approved for clinical use in recurrent bladder carcinomas, obstructing oesophageal tumours, and early carcinomas of the bladder, oesophagus, stomach, and tracheobronchial tree. PDT has also been shown to provide curative treatment of early carcinomas of the head and neck, including the oral cavity, pharynx, and larynx (Biel, 1995;Feyh, 1996). Initially PDT was tested in advanced cancers of the head and neck that were untreatable or refractory to conventional therapy, however these trials produced only limited success (Schuller et al, 1984;Wile et al, 1984). A recent retrospective review of the clinical data available for the treatment of head and neck neoplasia using photodynamic therapy indicated that complete response rates of 89.5% are achievable for early squamous cell carcinoma of the head and neck (Biel, 1998). Based on a range of photosensitizers and treatment modalities, cure rates of 95% and 80% were obtained for carcinoma in situ and T1 squamous cell carcinoma of the vocal chord and oral cavity/tongue respectively (follow up 70 months) (Biel, 1998).Most of the available photosensitizers, until recently, have been mixtures of porphyrins such as haematoporphyrin derivative and Photofrin (Quadralogic Technologies, Vancouver, Canada). The main problem with these first-generation photosensitizers is that of prolonged skin photosensitivity. Phototoxic incidences of 20-40% have been reported during follow-up of patients having received Photofrin, with a mean duration of skin photosensitivity exceeding 6 weeks (Dougherty et al, 1990).The use of 5-aminolaevulinic acid (ALA) represents a different strategy in the administration of photosensitizers. ALA itself is not the photo-active drug, but rather it induces, in situ, the synthesis of a pure endogenous porphyrin called protoporphyrin IX (PpIX). The formation of PpIX forms part of the haem synthesis pathway and all nucleated cells that use oxidative metabolism are probably capable of forming this photosensitizer. However, malignant tissue appears to preferentially accumulate PpIX, forming the basis of photodynamic therapy in cancer (Battle, 1993;Kennedy and Pottier, 1994). Intravenous ALA is rapidly cleared from the body, with no PpIX fluorescence within the skin or other body organs detectable after 24 h (Kennedy et al, 1991).Because of this reduced phototoxicity and excellent tumour localizing properties, ALA has been used with great success for the treatment of several neoplastic diseases, particularly of the skin, b...
