Safety and efficacy of peptide receptor radionuclide therapy with (177)Lu-DOTA(0)-Tyr(3)-octreotate in combination with amino acid solution infusion in Japanese patients with somatostatin receptor-positive, progressive neuroendocrine tumors

PURPOSE: Peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTA(0)-Tyr(3)-octreotate ((177)Lu-DOTATATE) is one of the most reliable treatments for unresectable, progressive neuroendocrine tumors (NETs) with somatostatin receptor expression. We have, for the first time, reported the results of the tolerability, safety, pharmacokinetics, dosimetry, and efficacy of this treatment for Japanese patients with NET. METHODS: Patients with unresectable, somatostatin receptor scintigraphy (SRS)-positive NETs were enrolled in this phase I clinical trial. They were treated with 29.6 GBq of (177)Lu-DOTATATE (four doses of 7.4 GBq) combined with amino acid solution infusion plus octreotide long-acting release (LAR) 30 mg. The primary objective of this study was to evaluate the tolerability, safety, pharmacokinetics, and dosimetry of a single administration of this treatment in patients with SRS-positive NETs. RESULTS: Six Japanese patients (three men and three women; mean age 61.5 years; range 50–70 years) with SRS-positive unresectable NETs were recruited. (177)Lu-DOTATATE was eliminated from the blood in a two-phase manner. Cumulative urinary excretion of radioactivity was 60.1% (range 49.0%–69.8%) within the initial 6 h. The cumulative renal absorbed dose for 29.6 GBq of (177)Lu-DOTATATE was 16.8 Gy (range 12.0–21.2 Gy), and the biological effective dose was 17.0 Gy (range 12.2–21.5 Gy). Administration of (177)Lu-DOTATATE was well tolerated, with no dose-limiting toxicities. Grade 3 lymphopenia occurred in two (33.3%) cases, but there were no other severe toxicities. Four patients achieved partial response (objective response rate, 66.7%), one patient had stable disease, and one patient had progressive disease. CONCLUSION: PRRT with (177)Lu-DOTATATE was well-tolerated and showed good outcomes in Japanese patients with unresectable NETs. Peptide receptor radionuclide therapy, (177)Lu-DOTA(0)-Tyr(3)-octreotate . SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12149-021-01674-9.