VASCULAR-TARGETED PHOTODYNAMIC THERAPY IN ORGAN CONFINED PROSTATE CANCER -REPORT OF A NOVEL PHOTOSENSITISER

Abstract

Introduction & Objectives Photodynamic Therapy (PDT) uses a photosensitising drug, activated by single wavelength light from a laser to cause localised necrosis. Tookad is a vascular acting photosensitiser which is activated by 763 nm light. It has a short drug light interval, so that both drug and light are given in a single session. Due to rapid clearance, it has no skin phototoxicity after 3 hours. Vascular-Targeted Photodynamic therapy (VTP) with Tookad (WST09) has been evaluated in patients with post-radiotherapy prostate cancer recurrence. Here we report the use of Tookad VTP in the previously untreated prostate. The effect of different light doses with a constant drug dose was evaluated using gadolinium-enhanced MRI at 1 week. Material & Methods Under general anaesthetic, using transrectal ultrasound guidance and a perineal template, two hollow, clear plastic needles were inserted into each of the right and left lobes of the prostate. On each side, the needles held one optical delivery fibre, and one optical detection fibre. Optical detectors were also placed within catheters in the urethra and rectum to monitor light levels throughout the light delivery phase. Once needle positions were finalised, an infusion of 2 mg/kg Tookad was given over 20 minutes. After the infusion began, the light dose was given. The light dose was escalated throughout the study, with a minimum of 50 J/cm, and a maximum of 300 J/cm at a power of either 150 or 200 mW. The active length of the diffuser was chosen to leave a 5 mm margin at the base and apex of the prostate. A dynamic gadolinium-enhanced MRI was performed prior to and 1 week after the VTP procedure. PSA was measured prior to and at 1, 3 and 6 months after VTP. Results Eleven men have undergone the Tookad VTP procedure and 1 week MRI to date. Prostate tissue necrosis, seen as absence of uptake of gadolinium, was observed in men receiving a light dose of 150 J/cm or more. The volume of necrosis varied with the light dose per cm, and the total light dose, but all patients had a PSA reduction at 1 or 3 months. All patients had a successful catheter removal the day after Tookad VTP, with four experiencing transient irritative urinary symptoms. Nine patients had a transient elevation of gamma GT and transaminases which resolved spontaneously within two weeks. Conclusions The Tookad VTP procedure is a promising minimally invasive treatment for prostate cancer. It can cause necrosis, as shown by lack of uptake of gadolinium on dynamic MRI at 1 week. This is accompanied by a PSA reduction. The procedure itself is safe and well tolerated. The study will continue using multiple optical fibres in each lobe.