m-THPC photodynamic therapy for head and neck cancer

Dilkes, M. G.; Dejode, M.; Rowntree-Taylor, A.; Mcgilligan, J. A.; Kenyon, Guy; McKelvie, P.

doi:10.1007/bf02161289

Cited by 75 publications

(41 citation statements)

References 15 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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“…Recently, mTHPC has shown to be a very effective photosensitizer in various tumour models and clinical trials (Ris et al, 1991;Lofgren et al, 1994;Peng et al, 1995;Dilkes et al, 1996;Grosjean et al, 1996;Mlkvy et al, 1997), with possible preferential uptake in a colon carcinoma in mice compared to liver concentrations (Whelpton et al, 1995). Furthermore, mTHPC drug and light doses needed to induce tumour necrosis are much lower than that of HpD (Berenbaum et al, 1986).…”

mentioning

confidence: 99%

Effective treatment of liver metastases with photodynamic therapy, using the second-generation photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC), in a rat model

et al. 1999

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SummaryThe only curative treatment for patients with liver metastases to date is surgery, but few patients are suitable candidates for hepatic resection. The majority of patients will have to rely on other treatment modalities for palliation. Photodynamic therapy (PDT) could be a selective, minimally invasive treatment for patients with liver metastases. We studied PDT in an implanted colon carcinoma in the liver of Wag/Rij rats, using the photosensitizer meta-tetra(hydroxyphenyl)chlorin (mTHPC). mTHPC tissue kinetics were studied using ex vivo extractions and in vivo fluorescence measurements. Both methods showed that mTHPC kinetics were different for liver and tumour tissue. After initial high levels at 4 h after administration (0.1 and 0.3 mg kg -1 ) mTHPC in liver tissue decreased rapidly in time. In tumour tissue no decrease in photosensitizer levels occurred, with mTHPC remaining high up to 48 h after administration. Both concentration data and fluorescence data showed an increase in tumour to liver ratios of up to 6.3 and 5.0 respectively. Illumination with 652 nm (15 J) resulted in extensive damage to tumour tissue, with necrosis of up to 13 mm in diameter. Damage to normal liver tissue was mild and transient as serum aspartate aminotransferase and alanine aminotransferase levels normalized within a week after PDT treatment. Long-term effects of mTHPC-PDT were studied on day 28 after treatment. Regardless of drug dose and drug-light interval, PDT with mTHPC resulted in complete tumour remission in 27 out of 31 treated animals (87%), with only four animals in which tumour regrowth was observed. Non-responding tumours proved to be significantly larger (P < 0.001) in size before PDT treatment. This study demonstrates that mTHPC is retained in an intrahepatic tumour and that mTHPC-PDT is capable of inducing complete tumour remission of liver tumours.

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“…A very important aspect of this process is survival of the surrounding normal tissues. Additionally, rapid migration of cells and healing must stay undisturbed, no ulceration or fibrosis should appear [28].…”

Section: Cancer Therapymentioning

confidence: 99%