TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer

被引:125
作者
Azzouzi, Abdel-Rahmene [1 ]
Barret, Eric [2 ]
Moore, Caroline M. [3 ]
Villers, Arnaud [4 ]
Allen, Clare [3 ]
Scherz, Avigdor [5 ]
Muir, Gordon [6 ]
de Wildt, Michel [7 ]
Barber, Neil J. [8 ]
Lebdai, Souhil [1 ]
Emberton, Mark [3 ]
机构
[1] Univ Hosp, Angers, France
[2] IMM, Paris, France
[3] Univ Coll London Hosp, London, England
[4] Univ Hosp Lille, Lille, France
[5] Weizmann Inst Sci, IL-76100 Rehovot, Israel
[6] Kings Coll Hosp London, London, England
[7] Catharina Hosp, Eindhoven, Netherlands
[8] Frimley Pk Hosp, Surrey, England
关键词
vascular; photodynamic; VTP; focal therapy; TOOKAD((R)); Soluble; prostate; PD-BACTERIOPHEOPHORBIDE TOOKAD; PHOTOSENSITIZER; TRENDS; WST11;
D O I
10.1111/bju.12265
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
Objectives To evaluate the optimal treatment conditions and effects of TOOKAD((R)) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD((R)) Soluble VTP treatment in patients with localised prostate cancer. Patients and Methods Men (aged > 18 years) diagnosed with localised prostate cancer, who were suitable for active surveillance, were invited to take part in the study. Patients who had received prior or current treatment for their cancer were excluded. There were two parts to the study: in part one, patients were assigned to one of two treatment groups based on the size of their prostates (patients with prostate size < 60 mL would receive 4 mg/kg TOOKAD((R)) Soluble and patients with prostate size >= 60 mL would receive 6 mg/kg TOOKAD((R)) Soluble both activated with 200 J/cm light). In part two, patients were assigned to one of two treatment groups based on predefined criteria and received either 4 or 6 mg/kg TOOKAD((R)) Soluble and 200 or 300 J/cm light. VTP was conducted under general anaesthesia using TOOKAD((R)) Soluble administered intravenously and activated by light-diffusing fibres within the prostate via the perineum. Follow-up was conducted for 6 months. Magnetic resonance imaging (MRI) carried out at 1 week after VTP and transrectal prostate biopsy at 6 months were the key endpoints. Adverse event (AE) recording and patient-reported outcome measures were collected. Results In all, 86 patients were enrolled in the study and 85 patients received treatment. Of the 85 treated patients, one patient discontinued (due to withdrawal of consent). At 6 months, 61/83 (74%) patients who underwent prostate biopsy had histopathology that was negative for prostate cancer (95% confidence interval (CI) 62.7-82.6%). Considering patients who received 4 mg/kg TOOKAD((R)) Soluble and 200 J/cm light (unilateral), which are considered optimal treatment parameters, 38/46 (83%) patients had histopathology from the biopsies that was negative for prostate cancer at 6 months (95% CI 68.6-92.2%; P < 0.001). The mean percentage of necrosis of the targeted prostate tissue at 7 days after VTP was 78% overall (83 patients) with extraprostatic necrosis reported in 76% (63/83) of patients. Considering patients who received 4 mg/kg TOOKAD((R)) Soluble and 200 J/cm light (unilateral), the mean 7-day necrosis percentage was 88% (46 patients) with extraprostatic necrosis reported in 72% (33/46) of patients. All occurrences of extraprostatic necrosis were considered clinically acceptable and none were associated with any clinical sequelae. The mean percentage prostate necrosis at 7 days was statistically significantly higher (P < 0.001) in patients treated with a therapeutic light density index (LDI) of >= 1 than those treated with a LDI of < 1. The percentage of patients with negative biopsies at 6 months was also higher in patients treated with a therapeutic LDI of >= 1 than those treated with a LDI of < 1 (78.6% and 63.0%, respectively). In all, 87% (75/86) of patients reported at least one treatment-emergent AE during the study. Most AEs were mild or moderate in intensity and considered related to the technical procedures of the study. No treated patients had hypotension or discontinued due to AEs. Eight patients (9.3%) had serious AEs; none resulted in discontinuation from the study. Conclusions Biopsy data, post-treatment dynamic contrast-enhancement MRI at 1 week after VTP and analysis of the safety data have shown that 4 mg/kg TOOKAD((R)) Soluble and 200 J/cm light are the optimal treatment conditions for the VTP procedure resulting in > 80% of patients treated with this regimen having a negative biopsy at 6 months. Overall, the treatment was well tolerated and exhibited early signs of efficacy for minimally invasive focal treatment of localised prostate cancer.
引用
收藏
页码:766 / 774
页数:9
相关论文
共 19 条
[1]
Focal therapy for localised unifocal and multifocal prostate cancer: a prospective development study [J].
Ahmed, Hashim U. ;
Hindley, Richard G. ;
Dickinson, Louise ;
Freeman, Alex ;
Kirkham, Alex P. ;
Sahu, Mahua ;
Scott, Rebecca ;
Allen, Clare ;
Van der Meulen, Jan ;
Emberton, Mark .
LANCET ONCOLOGY, 2012, 13 (06) :622-632
[2]
[Anonymous], ADV UROLOGY
[3]
Photocatalytic Generation of Oxygen Radicals by the Water-Soluble Bacteriochlorophyll Derivative WST11, Noncovalently Bound to Serum Albumin [J].
Ashur, Idan ;
Goldschmidt, Ruth ;
Pinkas, Iddo ;
Salomon, Yoram ;
Szewczyk, Grzegorz ;
Sarna, Tadeusz ;
Scherz, Avigdor .
JOURNAL OF PHYSICAL CHEMISTRY A, 2009, 113 (28) :8027-8037
[4]
A model to estimate the outcome of prostate cancer photodynamic therapy with TOOKAD Soluble WST11 [J].
Betrouni, Nacim ;
Lopes, Renaud ;
Puech, Philippe ;
Colin, Pierre ;
Mordon, Serge .
PHYSICS IN MEDICINE AND BIOLOGY, 2011, 56 (15) :4771-4783
[5]
Novel water-soluble bacteriochlorophyll derivatives for vascular-targeted photodynamic therapy: Synthesis, solubility, phototoxicity and the effect of serum proteins [J].
Brandis, A ;
Mazor, O ;
Neumark, E ;
Rosenbach-Belkin, V ;
Salomon, Y ;
Scherz, A .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2005, 81 (04) :983-993
[6]
How much does Gleason grade of follow-up biopsy differ from that of initial biopsy in untreated, Gleason score 4-7, clinically localized prostate cancer? [J].
Choo, R. ;
Danjoux, C. ;
Morton, G. ;
Szumacher, E. ;
Sugar, L. ;
Gardner, S. ;
Kim, M. ;
Choo, C. M. ;
Klotz, L. .
PROSTATE, 2007, 67 (15) :1614-1620
[7]
Contemporary trends in low risk prostate cancer: Risk assessment and treatment [J].
Cooperberg, Matthew R. ;
Broering, Jeannette M. ;
Kantoff, Philip W. ;
Carroll, Peter R. .
JOURNAL OF UROLOGY, 2007, 178 (03) :S14-S19
[8]
Time Trends and Local Variation in Primary Treatment of Localized Prostate Cancer [J].
Cooperberg, Matthew R. ;
Broering, Jeanette M. ;
Carroll, Peter R. .
JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (07) :1117-1123
[9]
EAU Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Treatment of Clinically Localised Disease [J].
Heidenreich, Axel ;
Bellmunt, Joaquim ;
Bolla, Michel ;
Joniau, Steven ;
Mason, Malcolm ;
Matveev, Vsevolod ;
Mottet, Nicolas ;
Schmid, Hans-Peter ;
van der Kwast, Theo ;
Wiegel, Thomas ;
Zattoni, Filliberto .
EUROPEAN UROLOGY, 2011, 59 (01) :61-71
[10]
Studies of a vascular-acting photosensitizer, Pd-bacteriopheophorbide (Tookad), in normal canine prostate and spontaneous canine prostate cancer [J].
Huang, Z ;
Chen, Q ;
Luck, D ;
Beckers, J ;
Wilson, BC ;
Trncic, N ;
LaRue, SM ;
Blanc, D ;
Hetzel, FW .
LASERS IN SURGERY AND MEDICINE, 2005, 36 (05) :390-397