Radioligand therapy (RLT) with 177Lu-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 177Lu-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 177Lu-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 177Lu-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.
European journal of nuclear medicine and molecular imaging. 2020 May 20 [Epub ahead of print]
Giovanni Paganelli, Anna Sarnelli, Stefano Severi, Maddalena Sansovini, Maria Luisa Belli, Manuela Monti, Flavia Foca, Monica Celli, Silvia Nicolini, Elisa Tardelli, Irene Marini, Federica Matteucci, Melchiore Giganti, Valentina Di Iorio, Ugo De Giorgi
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., 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., Dipartimento di Morfologia, Chirurgia e Medicina Sperimentale, Università di Ferrara, Ferrara, Italy.