Photodynamic Therapy for Oesophageal Carcinoma

Barrett’s oesophagus is the replacement of the normal squamous epithelium of the lower oesophagus by columnar epithelium with intestinal metaplasia. It is estimated to occur in about one in 100 people and is the most important risk factor for development of oesophageal adenocarcinoma. ^1–3 The metaplastic epithelium can progress in a step-wise fashion through low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and on to frank malignancy.^1,4,5 The risk of carcinoma increases with the severity of dysplasia and length of the Barrett’s.^6–9 The estimated incidence of carcinoma developing in a patient with Barrett’s is one in 150 patient years, with a 30- to 125-fold increase over the general population.^6,10

Unfortunately, many patients are declined surgery because of advanced age, significant co-morbidities or advanced disease that requires palliation only. The purpose of treatment is to improve swallowing and nutritional intake, eliminate reflux, prevent aspiration and improve the quality of life.^11,12

Photodynamic therapy (PDT) is an endoscopic treatment that can be used to treat Barrett’s as well as early and advanced oesophageal carcinoma. It involves the administration of a photosensitive drug that preferentially accumulates within the dysplastic/ neoplastic tissues, followed by an endoscopy, when it is activated by a non-thermal light source – usually generated by a laser. An activated photosensitiser liberates its energy to molecular oxygen to produce singlet oxygen, a highly reactive and cytotoxic species that produces tissue injury and necrosis.¹³

Photosensitisers

Haematoporphyrin and its Derivatives
Haematoporphyrin derivative (HpD) was the first photosensitiser to be developed. It is a complex mixture of monomeric and oligomeric porphyrins. Removal of the monomeric component yields the oligomeric fraction in which dihaematoporphyrin ester and ether (DHE) are located. These are the clinically active components in Photofrin^®, the only commercially available photosensitiser licensed for use within the oesophagus.

Between 48 and 72 hours prior to endoscopy, Photofrin (2.5mg/kg) is administered by slow intravenous injection. The drug is taken up by tissue macrophages – throughout the reticuloendothelial system and skin – as well as neoplastic tissue.^14,15 Other tissues within the body rapidly clear the drug, effectively concentrating the drug at the site to be treated.

Photofrin demonstrates maximal light absorption and maximal excitation at 405nm (the Soret band). Despite this, red light at 630nm is used, resulting in lesser drug activation, as this wavelength allows for deeper tissue penetration.

The biggest disadvantage of treatment is prolonged photosensitivity, which may last for several weeks because the drug is retained by skin macrophages for up to three months.^16,17 The second-generation photosensitisers 5-aminolaevulinic acid (5-ALA) and m-tetrahydroxyphenyl chlorin (m-THPC) have been employed in an attempt to overcome this problem.