title: Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response.
abstract: OBJECTIVE
  Tookad is a novel intravascular photosensitizer. When activated by 763 nm light, it destroys tumors by damaging their blood supply. It then clears rapidly from the circulatory system. To our knowledge we report the first application of Tookad vascular targeted photodynamic therapy in humans. We assessed the safety, pharmacokinetics and preliminary treatment response as a salvage procedure after external beam radiation therapy.
  
  
  METHODS
  Patients received escalating drug doses of 0.1 to 2 mg/kg at a fixed light dose of 100 J/cm or escalated light doses of 230 and 360 J/cm at the 2 mg/kg dose. Four optical fibers were placed transperineally in the prostate, including 2 for light delivery and 2 for light dosimetry. Treatment response was assessed primarily by hypovascular lesion formation on contrast enhanced magnetic resonance imaging and transrectal ultrasound guided biopsies targeting areas of lesion formation and secondarily by serum prostate specific antigen changes.
  
  
  RESULTS
  Tookad vascular targeted photodynamic therapy was technically feasible. The plasma drug concentration was negligible by 2 hours after infusion. In the drug escalation arm 3 of 6 patients responded, as seen on magnetic resonance imaging, including 1 at 1 mg/kg and 2 at 2 mg/kg. The light dose escalation demonstrated an increasing volume of effect with 2 of 3 patients in the first light escalation cohort responding and all 6 responding at the highest light dose with lesions encompassing up to 70% of the peripheral zone. There were no serious adverse events, and continence and potency were maintained.
  
  
  CONCLUSIONS
  Tookad vascular targeted photodynamic therapy salvage therapy is safe and well tolerated. Lesion formation is strongly drug and light dose dependent. Early histological and magnetic resonance imaging responses highlight the clinical potential of Tookad vascular targeted photodynamic therapy to manage post-external beam radiation therapy recurrence.
authors.affiliation: Department of Surgical Oncology, Ontario Cancer Institute/Princess Margaret Hospital/University Health Network, Toronto, Ontario, Canada. john.trachtenberg@utoronto.ca
authors.forename: J
authors.initials: J
authors.lastname: Trachtenberg
authors.forename: A
authors.initials: A
authors.lastname: Bogaards
authors.forename: R A
authors.initials: RA
authors.lastname: Weersink
authors.forename: M A
authors.initials: MA
authors.lastname: Haider
authors.forename: A
authors.initials: A
authors.lastname: Evans
authors.forename: S A
authors.initials: SA
authors.lastname: McCluskey
authors.forename: A
authors.initials: A
authors.lastname: Scherz
authors.forename: M R
authors.initials: MR
authors.lastname: Gertner
authors.forename: C
authors.initials: C
authors.lastname: Yue
authors.forename: S
authors.initials: S
authors.lastname: Appu
authors.forename: A
authors.initials: A
authors.lastname: Aprikian
authors.forename: J
authors.initials: J
authors.lastname: Savard
authors.forename: B C
authors.initials: BC
authors.lastname: Wilson
authors.forename: M
authors.initials: M
authors.lastname: Elhilali
mesh_terms: D001429:Bacteriochlorophylls / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001706:Biopsy; D001918:Brachytherapy / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy; D010778:Photochemotherapy / Q000379:methods*; D011467:Prostate / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000098:blood supply / Q000628:therapy*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D001429:Bacteriochlorophylls; C456120:palladium-bacteriopheophorbide; D017430:Prostate-Specific Antigen