Erectile function after WST11 vascular-targeted photodynamic therapy for low-risk prostate cancer treatment.

Vascular-targeted photodynamic therapy (VTP) using padeliporfin is currently assessed as a low-risk prostate cancer (LRPCa) treatment. The aim of this study was to assess erectile function outcomes of VTP for LRPCa treatment. We prospectively included all patients treated with VTP for LRPCa. The primary endpoint was the post-treatment International Index of Erectile Function score (IIEF5 score) evolution (at 6 months, 12 months, and then every year for 5 years). Secondary endpoints were the need of erectile dysfunction (ED) treatment and its efficacy. Eighty-two men were included. The median follow-up was 68 (range: 6-89) months. There was a 3-point significant decrease in the median IIEF5 score between baseline and at 6 months post-VTP (23 [range: 1-25] vs 20 [range: 1-25], P = 0.005). There was a 1-point decrease at 1 year and 2 years post-VTP compared to baseline (22 [range: 2-25] and 22 [range: 0-25], P < 0.005). There was no significant difference at 3, 4, and 5 years compared to baseline. Twenty-seven (32.9%) patients received ED treatment: phosphodiesterase type-5 inhibitors (PDEI5; n = 18), intracavernous injections (ICI; n = 9), and intra-urethral gel (n = 1). The median IIEF5 score statistically significantly increased after ED treatment (7 [range: 0-24] vs 21 [range: 1-25], P < 0.001). ED treatment was efficient for 75% of the patients. There was no statistically significant difference between IIEF5 score at baseline and after ED treatment (P = 0.443). Forty-six patients were totally potent before VTP and among them, 13 needed ED treatment post-VTP with a success rate of 69.2%. VTP induced minimal changes in erectile function with a 3-point and a 1-point reduction in the IIEF5 score at 6 months and at 1 year, respectively. When required, ED treatment was efficient.

Treatment of localized prostate cancer using WST-09 and WST-11 mediated vascular targeted photodynamic therapy-A review.

BACKGROUND: Photodynamic therapy (PDT) is well known for its direct cytotoxicity of the free radical-producing photochemical reaction, indirect mechanisms of action including modulation of intrinsic anti-tumour immune activity, and occlusion of pathologically altered tumour vessels leading to tumour ischaemia. The aim of this work is to critically review the evidence base for the use of vascular targeted PDT (VTP) to treat low-risk prostate cancer, and to discuss perspectives and challenges yet to be overcome. A brief general overview of focal prostate cancer therapy was provided, followed by a discussion of both basic and clinical research pertaining to prostate cancer VTP, with a focus on the palladium-based WST-09 and WST-11 photosensitisers. MATERIALS AND METHOD: Literature on VTP for prostate cancer with the fallowing medical subject headings search terms: prostate cancer, photodynamic therapy, vascular targeted photodynamic therapy, bacteriopheophorbide were reviewed. The articles were selected by their relevance to the topic. RESULTS: The clinical and basic research data available to date show much promise for WST-09, and WST-11 based VTP eventually joining the standard urologist's armamentarium against prostate cancer. With good reported tolerability and efficacy VTP can be proposed as an intermediate treatment for local low risk disease, halfway between watchful waiting and radical therapy.

[Photodynamic therapy: principles and therapeutic indications]. / Principes et applications thérapeutiques de la photothérapie dynamique.

Photodynamic therapy consists in destroying a tumoral or a non tumoral tissue by the effect of both a photosensitizing molecule and a laser light. This simple concept has needed numerous years in order to be used in routine treatments with both photosensitizers and laser light delivered optimally. Researches in chemistry lead to new porphyrin and bacteriochlorophyl derivatives which alleviate the decrease of light absorption by endogenous molecules and in consequence allow a deeper light penetration. Short half-life of these compounds allows an easier treatment monitoring. In parallel, improvements in both laser technology and fibers allow new indications in various pathologies. First applications took place in treatment of respiratory, digestive and urologic cancers. The biggest success to date is recorded in ophthalmology with the treatment of age related macular degeneration. New approaches are explored and clinical studies are ongoing.

Selection of dosing regimen with WST11 by Monte Carlo simulations, using PK data collected after single IV administration in healthy subjects and population PK modeling.

WST11, a novel generation of photo sensitizers to be used for vascular-targeted phototherapy (VTP), is effective at short interval between injection and illumination and it is expected to enable selective destruction of neovasculature with minimal side effects or skin photo toxicity. This study was conducted to evaluate the clinical and laboratory safety, tolerability and pharmacokinetic profile of WST11 given as a single intravenous administration (1.25, 2.5, 5, 7.5, 10, or 15 mg/kg) during an escalating dose study in healthy male subjects. This article describes WST11 population pharmacokinetic modeling and simulations performed to optimize the IV infusion-dosing regimen in combination with illumination, the target PK profile being plateau concentrations during approximately 30 min. The study included 42 healthy male subjects, administered 1.25, 2.5, 5, 7.5, 10, or 15 mg/kg as a 10-min IV infusion. A population pharmacokinetic model was developed using nonlinear mixed effects modeling (NONMEM). Monte Carlo simulations of the population PK dataset (NONMEM) were performed to select series of dosing regimen which would result in a plateau of concentration lasting at least 30 min and allow laser illumination. A two-compartment model with nonlinear elimination best described the data. No demographic factor was shown to affect the WST11 pharmacokinetics. The clearance was shown to decreases with the dose administered, ranging from 6 L/h (dose of 79 mg) to 2 L/h (dose of 1110 mg). The duration of the infusion was estimated at 12 min. The volume of distribution of the central compartment was 3 L and the volume of the peripheral compartment was 1.15 L. The apparent inter-compartmental clearance was 0.137 L/h. The between subjects variability on clearance and on volume was low. Residual variability was moderate with a CV of 21%. Due to the dose effect on clearance and the rapid elimination, simulations showed that different dosing inputs are necessary: for 5 and 10 mg/kg BW, a sufficiently good dosing scenario is to administer 80% of the dose over 5 min, 15% over 10 min and the remaining 5% over 10 min. For lower doses, the sequence 70% in 5 min/20% in 10 min/10% in 10 min is preferable. The pharmacokinetic profile of WST11 by IV administration would allow a treatment by laser illumination in good clinical conditions using controlled infusions. The study results do not indicate that the dose should be adjusted for body size. The only factor that determines the drug input profile is the dose level, since the elimination half-life decreases when the dose administered increases. The use of the population PK model for simulations has shown that, at dose level of 5 mg/kg or more, a loading dose of 80% dose given over 5 min followed by 15% of dose during 10 min and remained dose to give over 10 min would result in a favorable PK profile.