Determination of optimal drug dose and light dose index to achieve minimally invasive focal ablation of localised prostate cancer using WST11-vascular-targeted photodynamic (VTP) therapy.
OBJECTIVE
To determine the optimal drug and light dose for prostate ablation using WST11 (TOOKAD Soluble) for vascular-targeted photodynamic (VTP) therapy in men with low-risk prostate cancer.


METHODS
In all, 42 men with low-risk prostate cancer were enrolled in the study but two who underwent anaesthesia for the procedure did not receive the drug or light dose. Thus, 40 men received a single dose of 2, 4 or 6 mg/kg WST11 activated by 200 J/cm light at 753 nm. WST11 was given as a 10-min intravenous infusion. The light dose was delivered using cylindrical diffusing fibres within hollow plastic needles positioned in the prostate using transrectal ultrasonography (TRUS) guidance and a brachytherapy template. Magnetic resonance imaging (MRI) was used to assess treatment effect at 7 days, with assessment of urinary function (International Prostate Symptom Score [IPSS]), sexual function (International Index of Erectile Function [IIEF]) and adverse events at 7 days, 1, 3 and 6 months after VTP. TRUS-guided biopsies were taken at 6 months.


RESULTS
In all, 39 of the 40 treated men completed the follow-up. The Day-7 MRI showed maximal treatment effect (95% of the planned treatment volume) in men who had a WST11 dose of 4 mg/kg, light dose of 200 J/cm and light density index (LDI) of >1. In the 12 men treated with these parameters, the negative biopsy rate was 10/12 (83%) at 6 months, compared with 10/26 (45%) for the men who had either a different drug dose (10 men) or an LDI of <1 (16). Transient urinary symptoms were seen in most of the men, with no significant difference in IPSS score between baseline and 6 months after VTP. IIEF scores were not significantly different between baseline and 6 months after VTP.


CONCLUSIONS
Treatment with 4 mg/kg TOOKAD Soluble activated by 753 nm light at a dose of 200 J/cm and an LDI of >1 resulted in treatment effect in 95% of the planned treatment volume and a negative biopsy rate at 6 months of 10/12 men (83%).
Division of Surgery and Interventional Science, University College London, London, UK.
Caroline M
CM
Moore
CHU, Angers, France.
Abel-Rahmene
AR
Azzouzi
Institut Monsouris, Paris, France.
Eric
E
Barret
Hôpital Claude Huriez, CHRU, Lille, France.
Arnauld
A
Villers
King's College Hospital, London, UK.
Gordon H
GH
Muir
Frimley Park and Basingstoke Hospitals, Surrey, UK.
Neil J
NJ
Barber
Frimley Park and Basingstoke Hospitals, Surrey, UK.
Simon
S
Bott
Princess Margaret Hospital, Toronto, Canada.
John
J
Trachtenberg
Division of Surgery and Interventional Science, University College London, London, UK.
Nimalan
N
Arumainayagam
Steba Biotech, Paris, France.
Bertrand
B
Gaillac
Division of Surgery and Interventional Science, University College London, London, UK.
Clare
C
Allen
Plant Sciences, Weizmann Institute of Science, Rehovot, Israel.
Avigdor
A
Schertz
Division of Surgery and Interventional Science, University College London, London, UK.
Mark
M
Emberton
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001429:Bacteriochlorophylls / Q000008:administration & dosage / Q000627:therapeutic use; D001706:Biopsy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D011829:Radiation Dosage
D000970:Antineoplastic Agents; D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C503696:padeliporfin
TOOKAD; VTP; cancer; focal therapy; prostate