Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
BMC Cancer. 2023 Mar 23;23(1):268. doi: 10.1186/s12885-023-10725-5.
Prostate cancer patients with locoregional lymph node disease at diagnosis (N1M0) still have a limited prognosis despite the improvements provided by aggressive curative intent multimodal locoregional external beam radiation therapy (EBRT) with systemic androgen deprivation therapy (ADT). Although some patients can be cured and the majority of patients have a long survival, the 5-year biochemical failure rate is currently 29-47%. [Lu]Lu-PSMA-617 has shown impressive clinical and biochemical responses with low toxicity in salvage setting in metastatic castration-resistant prostate cancer. This study aims to explore the combination of standard EBRT and ADT complemented with a single administration of [Lu]Lu-PSMA-617 in curative intent treatment for N1M0 prostate cancer. Hypothetically, this combined approach will enhance EBRT to better control macroscopic tumour localizations, and treat undetected microscopic disease locations inside and outside EBRT fields.
The PROQURE-I study is a multicenter prospective phase I study investigating standard of care treatment (7 weeks EBRT and 3 years ADT) complemented with one concurrent cycle (three, six, or nine GBq) of systemic [Lu]Lu-PSMA-617 administered in week two of EBRT. A maximum of 18 patients with PSMA-positive N1M0 prostate cancer will be included. The tolerability of adding [Lu]Lu-PSMA-617 will be evaluated using a Bayesian Optimal Interval (BOIN) dose-escalation design. The primary objective is to determine the maximum tolerated dose (MTD) of a single cycle [Lu]Lu-PSMA-617 when given concurrent with EBRT + ADT, defined as the occurrence of Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 grade three or higher acute toxicity. Secondary objectives include: late toxicity at 6 months, dosimetric assessment, preliminary biochemical efficacy at 6 months, quality of life questionnaires, and pharmacokinetic modelling of [Lu]Lu-PSMA-617.
This is the first prospective study to combine EBRT and ADT with [Lu]Lu-PSMA-617 in treatment naïve men with N1M0 prostate cancer, and thereby explores the novel application of [Lu]Lu-PSMA-617 in curative intent treatment. It is considered likely that this study will confirm tolerability as the combined toxicity of these treatments is expected to be limited. Increased efficacy is considered likely since both individual treatments have proven high anti-tumour effect as mono-treatments.
ClinicalTrials, NCT05162573 . Registered 7 October 2021.
尽管采用积极的根治性局部区域外照射治疗（EBRT）联合全身性去势治疗（ADT）可改善诊断时伴有局部区域淋巴结疾病（N1M0）的前列腺癌患者的预后，但这些患者的预后仍有限。[Lu]Lu-PSMA-617 在转移性去势抵抗性前列腺癌的挽救治疗中具有令人印象深刻的临床和生化反应，且毒性低。本研究旨在探讨标准 EBRT 和 ADT 联合单次[Lu]Lu-PSMA-617 治疗 N1M0 前列腺癌的疗效。假设这种联合方法将增强 EBRT 以更好地控制宏观肿瘤定位，并治疗 EBRT 场内外未检测到的微观疾病部位。
PROQURE-I 研究是一项多中心前瞻性 I 期研究，调查标准治疗（7 周 EBRT 和 3 年 ADT）联合在 EBRT 第 2 周给予单次（3、6 或 9GBq）系统[Lu]Lu-PSMA-617 的疗效。将纳入最多 18 例 PSMA 阳性 N1M0 前列腺癌患者。采用贝叶斯最优区间（BOIN）剂量递增设计评估添加[Lu]Lu-PSMA-617 的耐受性。主要目的是确定在 EBRT+ADT 联合治疗时单次[Lu]Lu-PSMA-617 的最大耐受剂量（MTD），定义为发生不良事件通用术语标准（CTCAE）v5.0 级 3 级或更高的急性毒性。次要目标包括：6 个月时的迟发性毒性、剂量学评估、6 个月时的初步生化疗效、生活质量问卷和[Lu]Lu-PSMA-617 的药代动力学模型。
这是第一项前瞻性研究，旨在将 EBRT、ADT 与[Lu]Lu-PSMA-617 联合应用于初治 N1M0 前列腺癌患者，从而探索[Lu]Lu-PSMA-617 在根治性治疗中的新应用。预计该研究将证实其耐受性，因为这些治疗的联合毒性预计有限。由于两种治疗方法作为单药治疗均已证明具有较高的抗肿瘤效果，因此预计疗效会增加。
ClinicalTrials，NCT05162573。于 2021 年 10 月 7 日注册。
