Effect of photodynamic therapy in combination with ionizing radiation on human squamous cell carcinoma cell lines of the head and neck

Abstract

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...

Optimizing Photodynamic Therapy:In vivoPharmacokinetics of Liposomalmeta-(Tetrahydroxyphenyl)Chlorin in Feline Squamous Cell Carcinoma

“…PDT has the potential to be a powerful treatment modality for cancer either applied solitary or in combination with chemotherapy (16), surgery (17), radiotherapy (18), or other strategies, such as hyperthermia (19). However, low selectivity, inconveniently long drug-light intervals, and prolonged generalized photosensitivity are problems encountered with this therapy modality.…”

Enhanced effects of aminolaevulinic acid-based photodynamic therapy through local hyperthermia in rat tumours

“…A number of investigations have been carried out to enhance the effects of ALA-PDT and have included the use of varying fluence rates and light fractionation (Messmann et al, 1995;de Bruijn et al, 1999;Iinuma et al, 1999), iron chelators (Curnow et al, 1998) and the use of ALA-esters (Peng et al, 1997). Other antitumour approaches include the combination of PDT with radiotherapy (Peng et al, 1997;Allman et al, 2000) or chemotherapy (Datta et al, 1997;Canti et al, 1998). Evidence is also available suggesting that the combination of PDT with hyperthermia (HT) may result in enhanced tumour response effects.…”

Feasibility of interstitial Doppler optical coherence tomography for in vivo detection of microvascular changes during photodynamic therapy

“…It can be applied alone or in conjunction with other treatments [27,28]. It has been shown PDT can damage tumor cells and/or tumor microvasculature, the latter causing reduced blood flow or permanent vessel occlusion [18,20], which may aid in tumor eradication through hypoxia and nutrient deficiency [29].…”