Photodynamic therapy using mTHPC for malignant disease in the oral cavity

Fan, Kathleen; Hopper, Colin; Speight, Paul M.; Buonaccorsi, Giovanni A.; Bown, Stephen G.

doi:10.1002/(sici)1097-0215(19970926)73:1<25::aid-ijc5>3.0.co;2-3

Cited by 117 publications

(66 citation statements)

References 20 publications

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“…Standard clinical protocols for Foscan PDT involve illumination with 20 -30 J cm À2 at 4 days after a drug dose of 0.15 mg kg À1 . Such schedules are clearly effective at controlling small superficial tumours at sites such as the oral cavity and upper aerodigestive tract (Dilkes et al, 1996;Grosjean and Savary, 1996;Fan et al, 1997;Savary et al, 1997) . However, very few clinical studies have systematically investigated the influence of changing the drug -light interval while keeping both drug and light dose constant.…”

Section: Discussionmentioning

confidence: 99%

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

et al. 2003

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Clinical photodynamic therapy (PDT) schedules are based on the assumption that optimum drug -light intervals are times at which there is a maximum differential between photosensitiser retention in the tumour and surrounding normal tissue. However, vascularmediated effects contribute to tumour destruction by PDT; therefore, plasma sensitiser levels and endothelial cell drug exposure could also be important determinants of PDT response. The purpose of this study was to investigate the influence of tumour, tissue and plasma concentrations of the photosensitiser Foscan s (meta-tetrahydroxyphenylchlorin, mTHPC) on PDT response. Groups of BalbC nude mice, bearing human mesothelioma xenografts (H-MESO1) were injected (i.v.) with a single dose of 14 C-labelled mTHPC, or with two doses, separated by 72 h. Drug levels in plasma, tumour and normal tissues were measured at 5 min to 120 h after drug administration. The PDT tumour and skin responses were evaluated by illuminating separate groups mice at intervals of 5 min to 120 h after injection of Foscan (nonlabelled). Drug levels in both tumour and skin increased during the first 24 h after a single injection, and remained almost constant for at least 120 h. The second injection produced a further, rapid increase in mTHPC levels in tumours and skin, with steady state being maintained from 20 min to 120 h. By contrast, PDT response of both tumours and skin were maximal for illumination at 1 -3 h after drug, with very little response when illumination was given 48 -120 h after drug. There was no significant correlation between tumour or skin drug level and PDT response. There was, however, a significant correlation between plasma drug levels and tumour or skin response, excluding an initial distribution time of 20 min. These studies demonstrate a pronounced disassociation between tumour drug levels and optimum drug -light intervals for PDT response with Foscan. We suggest that the PDT effect, in both tumours and normal tissues, is largely mediated via vascular damage and that the selectivity of PDT is not based on differential tumour drug uptake.

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Section: Discussionmentioning

confidence: 99%

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

et al. 2003

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“…For cancers of the oral cavity, the function and appearance of the mouth can be preserved without sacrificing the efficacy of tumour control (Fan et al, 1997;Hopper, 2000). Photodynamic therapy does not have the cumulative toxicity associated with ionising radiation and can be applied safely to previously irradiated tissues.…”

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confidence: 99%

Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer

et al. 2004

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Interstitial photodynamic therapy (IPDT) is a technique for applying photodynamic therapy (PDT) to internal tumours using light delivered via fibres inserted percutaneously. This phase I -II study assessed the safety and efficacy of IPDT for patients with persistent or recurrent head and neck cancer unsuitable for further treatment with surgery, radiotherapy or chemotherapy, recruited for 'last hope' salvage treatment. Patients were sensitised with 0.15 mg kg À1 mTHPC (meso-tetrahydroxyphenyl chlorin) 4 days prior to light delivery from fibres inserted directly into the target tumour (20 J per site at 652 nm) under image guidance. In all, 45 patients were treated. Nine achieved a complete response. Five are alive and free of disease 10 -60 months later. Symptomatic relief (mainly for bleeding, pain or tumour debulking) was achieved in a further 24. The median survival (Kaplan -Meier) was 16 months for the 33 responders, but only 2 months for the 12 nonresponders. The only serious complication was a carotid blow out 2 weeks after PDT. No loss of function was detected in nerves encased by treated tumours. Interstitial photodynamic therapy provides worthwhile palliation with few complications and occasional long-term survivors for otherwise untreatable advanced head and neck cancers. It is a treatment option worth adding to those available to integrated head and neck oncology teams.

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“…There are numerous ongoing studies aimed at development of 'new generation' photosensitizers, and many of these compounds show promise (Gomer, 1991;Pandey et al, 1995;Fan et al, 1997). Recently, there has been considerable interest in the formation of an endogenously produced photosensitizer, protoporphyrin IX (PPIX) (Malik and Lugaci, 1987;Kennedy and Pottier, 1992;Peng et al, 1997).…”

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confidence: 99%

δ-Aminolaevulinic acid-induced photodynamic therapy inhibits protoporphyrin IX biosynthesis and reduces subsequent treatment efficacy in vitro

Havens

Nguyen

et al. 1999

Br J Cancer

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Summary Recently, considerable interest has been given to photodynamic therapy of cancer using δ-aminolaevulinic acid to induce protoporphyrin IX as the cell photosensitizer. One advantage of this modality is that protoporphyrin IX is cleared from tissue within 24 h after δ-aminolaevulinic acid administration. This could allow for multiple treatment regimens because of little concern regarding the accumulation of the photosensitizer in normal tissues. However, the haem biosynthetic pathway would have to be fully functional after the first course of therapy to allow for subsequent treatments. Photosensitization of cultured R3230AC rat mammary adenocarcinoma cells with δ-aminolaevulinic acid-induced protoporphyrin IX resulted in the inhibition of porphobilinogen deaminase, an enzyme in the haem biosynthetic pathway, and a concomitant decrease in protoporphyrin IX levels. Cultured R3230AC cells exposed to 0.5 mM δ-aminolaevulinic acid for 27 h accumulated 6.07 × 10 -16 mol of protoporphyrin IX per cell and had a porphobilinogen deaminase activity of 0.046 fmol uroporphyrin per 30 min per cell. Cells cultured under the same incubation conditions but exposed to 30 mJ cm -2 irradiation after a 3-h incubation with δ-aminolaevulinic acid showed a significant reduction in protoporphyrin IX, 2.28 × 10 -16 mol per cell, and an 80% reduction in porphobilinogen deaminase activity to 0.0088 fmol uroporphyrin per 30 min per cell. Similar effects were evident in irradiated cells incubated with δ-aminolaevulinic acid immediately after, or following a 24 h interval, post-irradiation. There was little gain in efficacy from a second treatment regimen applied within 24 h of the initial treatment, probably a result of initial metabolic damage leading to reduced levels of protoporphyrin IX. These findings suggest that a correlation may exist between the δ-aminolaevulinic acid induction of porphobilinogen deaminase activity and the increase in intracellular protoporphyrin IX accumulation.

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Photodynamic therapy using mTHPC for malignant disease in the oral cavity

Cited by 117 publications

References 20 publications

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Foscan® uptake and tissue distribution in relation to photodynamic efficacy

Interstitial photodynamic therapy as salvage treatment for recurrent head and neck cancer

δ-Aminolaevulinic acid-induced photodynamic therapy inhibits protoporphyrin IX biosynthesis and reduces subsequent treatment efficacy in vitro

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