Phase I/II study of verteporfin photodynamic therapy in locally advanced pancreatic cancer

Abstract

Background:Patients with pancreatic cancer have a poor prognosis apart from the few suitable for surgery. Photodynamic therapy (PDT) produces localised tissue necrosis but previous studies using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC) caused prolonged skin photosensitivity. This study assessed a shorter acting photosensitiser, verteporfin.Methods:Fifteen inoperable patients with locally advanced cancers were sensitised with 0.4 mg kg−1 verteporfin. After 60–90 min, laser light (690 nm) was delivered via single (13 patients) or multiple (2 patients) fibres positioned percutaneously under computed tomography (CT) guidance, the light dose escalating (initially 5 J, doubling after each three patients) until 12 mm of necrosis was achieved consistently.Results:In all, 12 mm lesions were seen consistently at 40 J, but with considerable variation in necrosis volume (mean volume 3.5 cm3 at 40 J). Minor, self-limiting extrapancreatic effects were seen in multifibre patients. No adverse interactions were seen in patients given chemotherapy or radiotherapy before or after PDT. After PDT, one patient underwent an R0 Whipple's pancreaticoduodenectomy.Conclusions:Verteporfin PDT-induced tumour necrosis in locally advanced pancreatic cancer is feasible and safe. It can be delivered with a much shorter drug light interval and with less photosensitivity than with older compounds.

Duramycin-porphyrin conjugates for targeting of tumour cells using photodynamic therapy

“…A number of studies in the literature have investigated the effect of PDT on ovarian and pancreatic cancer in a variety of models including cell lines [61], 3D cell culture [62][63][64], transplanted mice [65,66] and Phase I/II human trials [67,68]. A benzoporphyrin derivative (BPD) at 0.25 μM was able to reduce cell viability and volume in the human ovarian carcinoma cell line OVCAR5 and penetrate well through OVCAR5 3D cell culture [62,63].…”

“…Treatment of this cell line with verteporfin at 250 nM with a light dose of 10 J/cm 2 was effective enough to induce complete cell death [61]. Verteporfin has been used successfully in a Phase I/II trial against advanced pancreatic cancer where it accumulated quickly in the target tissue, induced necrotic cell death and had a fast clearance via excretion in bile [68].…”

A Tumor Vascular‐Targeted Interlocking Trimodal Nanosystem That Induces and Exploits Hypoxia

“…VP‐mediated PDT has been approved for age‐related macular degeneration,2 and also investigated against multiple cancers 12…”

The Use of Photod Ynamic Therapy in the Domestic Oncology. (Review of the Litera Ture)

“…К настоящему времени зарубежом в различных меди-цинских Центрах по всему миру получены данные об эф-фективности ФДТ при лечении злокачественных опухолей поджелудочной железы, шейки матки, полости рта, про-статы, бронхов, кожи и других локализаций [2][3][4][5][6][7][8].…”