TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer
TOOKAD® Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer
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DOI：
10.1111/bju.12265
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发表时间：
2013-10-01
影响因子：
4.5
通讯作者：
Emberton, Mark
中科院分区：
文献类型：
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作者：
Azzouzi, Abdel-Rahmene;Barret, Eric;Emberton, Mark
目的探讨tokad （(R)）可溶性血管靶向光动力（VTP）治疗局限性前列腺癌的最佳治疗条件和效果。评价局部前列腺癌患者接受tokad （(R)）可溶性VTP治疗后的安全性和生活质量。本研究邀请适合主动监测的局限性前列腺癌患者和研究人员（年龄0 ~ 18岁）参加研究。之前或目前接受过癌症治疗的患者被排除在外。研究分为两部分：第一部分，患者根据前列腺大小分为两组(前列腺大小< 60 mL的患者接受4 mg/kg可溶性TOOKAD(（R))，前列腺大小>= 60 mL的患者接受6 mg/kg可溶性TOOKAD((R))，均以200 J/cm的光激活）。在第二部分中，患者根据预定义的标准被分配到两个治疗组中的一个，并接受4或6 mg/kg可溶性tokad （(R)）和200或300 J/cm光。VTP在全身麻醉下使用tokad （(R)）可溶性静脉给药，通过会阴通过前列腺内的光扩散纤维激活。随访6个月。VTP后1周的磁共振成像（MRI）和6个月的经直肠前列腺活检是关键终点。收集不良事件（AE）记录和患者报告的结果测量。结果86例患者入组，85例患者接受治疗。在85名接受治疗的患者中，1名患者停止治疗（由于撤回同意）。6个月时，61/83（74%）接受前列腺活检的患者的组织病理学结果为前列腺癌阴性（95%置信区间（CI） 62.7-82.6%）。考虑到接受4 mg/kg tokad （(R)）可溶性和200 J/cm光（单侧）治疗的患者被认为是最佳治疗参数，38/46（83%）患者在6个月时活检组织病理学显示前列腺癌阴性（95% CI 68.6-92.2%; P < 0.001）。VTP术后7天，靶前列腺组织坏死的平均百分比为78%（83例），其中76%（63/83）的患者报告前列腺外坏死。考虑到接受4 mg/kg tokad （(R)）可溶性和200 J/cm光（单侧）治疗的患者，平均7天坏死率为88%（46例），其中72%（33/46）的患者报告前列腺外坏死。所有前列腺外坏死的发生都被认为是临床可接受的，没有任何临床后遗症。治疗性光密度指数（LDI）为>= 1的患者7天前列腺坏死的平均百分比显著高于LDI < 1的患者（P < 0.001）。治疗性LDI为>= 1的患者6个月活检阴性的比例也高于LDI < 1的患者（分别为78.6%和63.0%）。总的来说，87%（75/86）的患者在研究期间报告了至少一次治疗性AE。大多数ae的强度为轻度或中度，被认为与研究的技术程序有关。没有治疗患者出现低血压或因不良反应而停药。严重不良事件8例（9.3%）；没有一例导致中止研究。活检数据、VTP术后1周治疗后动态对比增强MRI和安全性数据分析显示，4mg /kg tokad （(R)）可溶性和200 J/cm光照是VTP手术的最佳治疗条件，该方案治疗的80%患者在6个月时活检结果为阴性。总的来说，治疗耐受性良好，并表现出对局部前列腺癌微创局灶治疗有效的早期迹象。
ObjectivesTo 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 MethodsMen (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.ResultsIn 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.ConclusionsBiopsy 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.