Optimization of treatment parameters for Foscan®‐PDT of basal cell carcinomas

Betz, Christian; Rauschning, W.; Stranadko, Evgueni P.; Riabov, Mikhail V.; Albrecht, Volker; Nifantiev, Nikolay E.; Hopper, Colin

doi:10.1002/lsm.20632

Cited by 39 publications

(35 citation statements)

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“…One blatant example is Foscan ® , an ethanol/propylene glycol formulation of the PS temoporfin , which failed to achieve FDA approval for treatment of H&N cancers due to poor tumor selectivity and serious burns arising from lingering skin photosensitivity 14,15 . In such formulations involving surfactants and organic excipients, PS accumulation in tumors is not by any controllable mechanism.…”

Section: Introductionmentioning

confidence: 99%

A Cell-Targeted Photodynamic Nanomedicine Strategy for Head and Neck Cancers

et al. 2013

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Photodynamic Therapy (PDT) holds great promise for the treatment of head and neck (H&N) carcinomas where repeated loco-regional therapy often becomes necessary due to the highly aggressive and recurrent nature of the cancers. While interstitial light delivery technologies are being refined for PDT of H&N and other cancers, a parallel clinically relevant research area is the formulation of photosensitizers in nanovehicles that allow systemic administration yet preferential enhanced uptake in the tumor. This approach can render dual-selectivity of PDT, by harnessing both the drug and the light delivery within the tumor. To this end, we report on a cell-targeted nanomedicine approach for the photosensitizer silicon phthalocyanine-4 (Pc 4), by packaging it within polymeric micelles that are surface-decorated with GE11-peptides to promote enhanced cell-selective binding and receptor-mediated internalization in EGFR-overexpressing H&N cancer cells. Using fluorescence spectroscopy and confocal microscopy, we demonstrate in vitro that the EGFR-targeted Pc 4-nanoformulation undergoes faster and higher uptake in EGFR-overexpressing H&N SCC-15 cells. We further demonstrate that this enhanced Pc 4 uptake results in significant cell-killing and drastically reduced post-PDT clonogenicity. Building on this in vitro data, we demonstrate that the EGFR-targeted Pc 4-nanoformulation results in significant intra-tumoral drug uptake and subsequent enhanced PDT response, in vivo, in SCC-15 xenografts in mice. Altogether our results show significant promise towards a cell-targeted photodynamic nanomedicine for effective treatment of H&N carcinomas.

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Section: Introductionmentioning

confidence: 99%

A Cell-Targeted Photodynamic Nanomedicine Strategy for Head and Neck Cancers

et al. 2013

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“…When reducing the drug dose, a shorter DLI of approx. 24 h was suggested in the literature 9 . However, we could not find a significantly reduced DLI with our patients, at least not for the measurements on oral mucosa.…”

Section: Fluorescence Kineticsmentioning

confidence: 93%

“…Little is known, however, whether there is a need to adjust the time between drug application and PDT, the so-called drug-light-interval (DLI). Driven by also practical considerations, Betz et al 9 tested different DLI and found a good treatment efficiency at a DLI of 24 hours compared to the standard 72-96 hours for the treatment of basal cell carcinomas.…”

Section: Introductionmentioning

confidence: 98%

“…This comes not entirely unexpected, as Foscan is known to be a very potent photosensitizer, but shows only limited tumour selectivity and also does accumulate in human skin, albeit for a shorter time as porfimer sodium. It has therefore been suggested to reduce the Foscan dose and compensate the reduced drug dose with an increased light dose 8,9 . This is expected to reduce systemic side effects while maintaining the local phototoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Low dose mTHPC photodynamic therapy for cholangiocarcinoma

Stepp

Kniebühler

Pongratz

et al. 2013

Medical Laser Applications and Laser-Tissue Interactions VI

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Objective: Demonstration of whether a low dose of mTHPC (temoporfin , Foscan) is sufficient to induce an efficient clinical response in palliative PDT of non-resectable cholangiocarcinoma (CC), while showing a low side effect profile as compared to the standard Photofrin PDT. Materials and Methods: 13 patients (14 treatment sessions) with non-resectable CC were treated with stenting and PDT (3 mg Foscan per treatment, 0.032-0.063 mg/kg body weight, 652 nm, 50 J/cm). Fluorescence measurements were performed with a single bare fiber for 5/13 patients prior to PDT at the tumor site to determine the fluorescence contrast. For another 7/13 patients, long-term fluorescence-kinetics were measured on the oral mucosa to determine the time of maximal relative fluorescence intensity.Results: Foscan fluorescence could clearly be identified spectroscopically as early as 20 hours after administration. It was not significantly different between lesion and normal tissue within the bile duct. Fluorescence kinetics assessed at the oral mucosa were highest at 72-96 hours after administration. The DLI was therefore extended from 20 hours to approx. 70 hours for the last 5 patients treated. The treatment effect was promising with a median survival of 11 months for the higher grade tumors (Bismuth types III and IV). Local side effects occurred in one patient (pancreatitis), systemic side effects were much reduced compared to prior experience with Photofrin. Conclusion:Combined stenting and photodynamic therapy (PDT) performed with a low dose of Foscan results in comparable survival times relative to standard Photofrin PDT, while lowering the risk of side effects significantly.

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“…При локализации опухолей в области головы и шеи все боль-шее применение находят такие относительно новые тех-нологии, как криохирургия, лазерохирургия. Фотодина-мическая терапия (ФДТ) представляет собой новое на-правление в лечении злокачественных опухолей, осно-ванное на использовании повреждения патологических клеток в ходе фотохимической реакции, и является одним из перспективных методов лечения рака ЛОР-органов [2][3][4][5][6][7].…”

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