Temoporfin


  • Photosensitizer: Temoporfin
  • Tradename: Foscan®
  • Company Photosensitizer: Scotia Pharmaceuticals
  • Clinical Application: Head and neck cancer, oesophageal cancer, Barrett’s oesophagus, gastric and prostate cancer, hyperplasia, sterilization, antibiotic
  • Wavelength (nm): 652
  • Extinction Coefficient (M-1 cm-1): 3.0 104
  • Mode of Delivery: polyethylene glycol, ethanol, water
  • Delivery vehicle: Lipid emulsion
  • Typical Dose (mg kg-1): 0.1–0.3
  • Light Dose (J cm-2): 8–12
  • Time Post-Injection: 24–48 h
  • Duration of Skin Photosensitivity: Up to 6 weeks



Temoporfin or tetra(m-hydroxyphenyl) chlorin (mTHPC)[86], under the tradename Foscan™, is being marketed by Scotia Pharmaceuticals (Guildford, Surrey, UK) as a new second-generation photosensitizer for PDT. Phase III clinical trials have begun in Europe and the US using Foscan against head and neck cancers. Trial work has concentrated on this area as the conventional treatments are difficult, ineffective and disfiguring.

Recent press releases from the company state that Foscan has been given fast-track designation by the FDA for the palliative treatment of recurrent, refractory and second primary squamous cell carcinomas of the head and neck in patients considered to be incurable using surgery or radiotherapy, the file submission being expected soon. Foscan is also in clinical trials for latestage oesophageal cancer and dysplasia in Barrett’s oesophagus. Future trials using this photosensitizer in Europe, the US and the Far East against malignant and non-malignant diseases are anticipated and will include trials against gastric and prostatic cancers, hyperplasia, field sterilization after cancer surgery and for the control of antibiotic-resistant bacteria[87].

In addition, topical formulations of temoporfin are being developed to compete with ALA against skin cancers and other dermatological conditions. Temoporfin could be one of the most phototoxic of all the second-generation photosensitizers currently being investigated. It requires very low doses (as little as 0.1 mg kg-1) as well as an unusually low light dose (as low as 10 J cm-2), making it 100-fold more photoactive than Photofrin, which requires drug doses of 2–5 mg kg-1 and light doses of 100–200 J cm-2.

The reasons behind this exceptionally high activity are not fully known. While improved optical properties and singlet oxygen quantum yields can partially explain this increased phototoxicity, it appears the explanation resides in the subtumoral and subcellular localization of the compound.

While on intravenous administration, lipophilic sensitizers bind to lipoproteins and hydrophilic compounds to serum albumin, temoporfin can bind to an unknown plasma protein presumably involving the polyethylene glycol (PEG) vehicle, which might produce differences in subcellular localization. Furthermore, the interaction with a plasma protein other than albumin or lipoproteins could explain the novel pharmacokinetics. The immediate peak in plasma drug levels produced by intravenous administration is followed by a second plasma peak several hours later[88] and this could be a factor in the high phototoxicity of this compound.

Temoporfin

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