Paganelli Giovanni, Sarnelli Anna, Severi Stefano, Sansovini Maddalena, Belli Maria Luisa, Monti Manuela, Foca Flavia, Celli Monica, Nicolini Silvia, Tardelli Elisa, Marini Irene, Matteucci Federica, Giganti Melchiore, Di Iorio Valentina, De Giorgi Ugo
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
Unità Operativa Complessa di Medicina Nucleare, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Eur J Nucl Med Mol Imaging. 2020 Dec;47(13):3008-3017. doi: 10.1007/s00259-020-04856-1. Epub 2020 May 20.
Radioligand therapy (RLT) with Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate cancer (mCRPC). The present study was designed to define the safety and initial response to a minimal effective injected activity/cycle of Lu-PSMA-617 in mCRPC patients. New protective agents for salivary glands and kidney were co-administered and dosimetry was carried out.
A prospective single-arm, open label phase II study on mCRPC was activated at our institute in April 2017. Patients with histologically confirmed advanced mCRPC previously treated with standard life-prolonging agents were enrolled. Folic polyglutamate tablets were orally administered as parotid gland protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake before the injection of 3.7-5.5 GBq of Lu-PSMA-617 repeated four times at interval of 8 weeks. The adsorbed dose calculation was performed with MIRD formalism (OLINDA/EXM software). The Bryant and Day design was used to estimate the sample size taking account of both activity and toxicity.
Forty-three eligible patients were evaluated for toxicity and initial response. Dosimetry was carried out in 13 patients. Two (4.8%) patients had G3 and 8 (19.5%) had G2 hematological toxicity. Only 3 (6.9%) patients had mild G1 salivary gland toxicity and 8 (19.5%) had G1 renal toxicity. A decrease of ≥ 30% in prostate-specific antigen (PSA) was achieved after the first cycle in 17 (40.5%) patients, of whom 13 had a PSA decline of >50% after the second cycle. The median adsorbed doses were 0.65 mGy/MBq (range 0.33-2.63) for parotid glands, 0.42 mGy/MBq (0.14-0.81) for kidneys, 0.036 mGy/MBq (0.023-0.067) for red marrow, and 0.038 mGy/MBq (0.018-0.135) for the whole body.
In advanced, heavily pre-treated mCRPC patients, 3.7 GBq/cycle of Lu-PSMA-617 was safe and produced early biochemical and imaging responses at PSMA whole-body scan post injection. Dosimetry of salivary glands suggests that the co-administration of polyglutamate tablets may reduce salivary gland uptake.
EU Clinical Trials Register No.: 2016-002732-32; NCT03454750. Collection and assembly of data: April 2017 and February 2019.
使用Lu-PSMA-617进行放射性配体治疗（RLT）是转移性去势抵抗性前列腺癌（mCRPC）患者的一种有前景的选择。本研究旨在确定mCRPC患者中Lu-PSMA-617的最小有效注射活度/周期的安全性和初始反应。同时联合使用了新型唾液腺和肾脏保护剂，并进行了剂量测定。
2017年4月在我们研究所启动了一项关于mCRPC的前瞻性单臂、开放标签的II期研究。纳入组织学确诊的晚期mCRPC患者，这些患者先前接受过标准的延长生命药物治疗。口服叶酸聚谷氨酸片作为腮腺保护剂，并在注射3.7 - 5.5GBq的Lu-PSMA-617前静脉输注500mL 10%的甘露醇溶液以减少肾脏摄取，每8周重复注射4次。采用MIRD形式（OLINDA/EXM软件）进行吸收剂量计算。考虑到活度和毒性，使用Bryant和Day设计来估计样本量。
对43例符合条件的患者进行了毒性和初始反应评估。13例患者进行了剂量测定。2例（4.8%）患者出现3级血液学毒性，8例（19.5%）出现2级血液学毒性。仅3例（6.9%）患者出现轻度1级唾液腺毒性，8例（19.5%）出现1级肾脏毒性。17例（40.5%）患者在第一个周期后前列腺特异性抗原（PSA）下降≥30%，其中13例在第二个周期后PSA下降>50%。腮腺的中位吸收剂量为0.65mGy/MBq（范围0.33 - 2.63），肾脏为0.42mGy/MBq（0.14 - 0.81），红骨髓为0.036mGy/MBq（0.023 - 0.067），全身为0.038mGy/MBq（0.018 - 0.135）。
在晚期、经过大量前期治疗的mCRPC患者中，每周期3.7GBq的Lu-PSMA-617是安全的，并在注射后PSMA全身扫描时产生了早期生化和影像学反应。唾液腺剂量测定表明，联合使用聚谷氨酸片可能会减少唾液腺摄取。
欧盟临床试验注册号：2016 - 002732 - 32；NCT03454750。数据收集与汇总时间：2017年4月和2019年2月。
