First-in-Humans Study of the SSTR Antagonist 177Lu-DOTA-LM3 for Peptide Receptor Radionuclide Therapy in Patients with Metastatic Neuroendocrine Neoplasms: Dosimetry, Safety, and Efficacy
| Autor: | Richard P. Baum, Helmut R. Mäcke, Jingjing Zhang, Dirk Müller, Christiane Schuchardt |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Agonist medicine.medical_specialty Nausea medicine.drug_class Octreotide Gastroenterology 03 medical and health sciences 0302 clinical medicine Positron Emission Tomography Computed Tomography Internal medicine Organometallic Compounds medicine Humans Tissue Distribution Radiology Nuclear Medicine and imaging Clinical Investigation Adverse effect Aged 030304 developmental biology 0303 health sciences Leukopenia business.industry Cancer Common Terminology Criteria for Adverse Events Middle Aged medicine.disease Neuroendocrine Tumors 030220 oncology & carcinogenesis Radionuclide therapy medicine.symptom business Progressive disease |
| Zdroj: | J Nucl Med |
| ISSN: | 2159-662X 0161-5505 |
| DOI: | 10.2967/jnumed.120.258889 |
| Popis: | The objective of this study was to assess the safety, dosimetry, and efficacy of the (177)Lu-labeled somatostatin receptor (SSTR) antagonist DOTA-p-Cl-Phe-cyclo(d-Cys-Tyr-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)d-Tyr-NH(2) ((177)Lu-DOTA-LM3) in patients with metastatic neuroendocrine neoplasms (NENs). Methods: Fifty-one patients (aged 27–76 y; mean, 51.6 ± 13.9 y) with metastatic NENs underwent peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTA-LM3 between August 2017 and December 2019. The median administered activity per cycle was 6.1 ± 0.88 GBq (range, 2.8–7.4 GBq). (68)Ga-NODAGA-LM3 PET/CT was used for patient selection and follow-up after (177)Lu-DOTA-LM3 PRRT. Morphologic and molecular responses were evaluated in accordance with RECIST 1.1 and the criteria of the European Organisation for Research and Treatment of Cancer (EORTC). Treatment-related adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dosimetry was performed on 11 patients and compared with the SSTR agonist (177)Lu-DOTATOC in 247 patients undergoing PRRT on the same dosimetry protocol. Results: Higher uptake and a longer effective half-life were found for (177)Lu-DOTA-LM3 than for the agonist (177)Lu-DOTATOC in the whole body and in the kidneys, spleen, and metastases, resulting in higher mean absorbed organ and tumor doses. All patients tolerated therapy without any serious acute adverse effects. Mild nausea without vomiting was observed in 5 (9.8%) patients; no other symptoms were reported. The most severe delayed adverse event was Common Terminology Criteria (CTC)-3 thrombocytopenia in 3 (5.9%) patients. Neither CTC-4 thrombocytopenia nor CTC-3–4 anemia or leukopenia was observed after treatment. No significant decline in renal function was observed, nor was hepatotoxicity. According to RECIST 1.1, disease control could be reached in 40 patients (disease control rate, 85.1%) of the 47 patients monitored after (177)Lu-DOTA-LM3 PRRT, with a partial response in 17 (36.2%) and stable disease in 23 (48.9%), whereas 7 patients (14.9%) had progressive disease, and by EORTC criteria, there was complete remission in 2 patients (4.3%), partial remission in 21 (44.7%), stable disease in 18 (38.3%), and progressive disease in 6 (12.8%). Conclusion: The antagonist PRRT with (177)Lu-DOTA-LM3 could be administered without severe adverse effects and was well tolerated by most patients, with thrombocytopenia occurring in only a few. No other severe adverse effects were observed; in particular, there was no nephrotoxicity. The SSTR antagonist (177)Lu-DOTA-LM3 appears to be promising for PRRT, provides a favorable biodistribution and higher tumor radiation doses than SSTR agonists, and was effective in treating advanced metastatic NENs, especially in patients with low or no SSTR agonist binding, even achieving complete remission in some patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|