Peptide Receptor Radionuclide Therapy of Late-stage Neuroendocrine Tumor Patients with Multiple Cycles of 177Lu-DOTA-EB-TATE.

Purpose: This study aimed to evaluate the safety and efficacy of multiple cycles of 177Lu-DOTA-EB-TATE peptide receptor radionuclide therapy (PRRT) at escalating doses in neuroendocrine tumors (NETs). Methods: A total of 32 NET patients were randomly divided into 3 groups and treated with escalating doses: group A (1.17 ± 0.09 GBq/cycle); group B (1.89 ± 0.53 GBq/cycle); group C (3.97 ± 0.84 GBq/cycle). The treatment was planned up to three cycles. Treatment-related adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v.5.0). Treatment response was referred to European Organization for Research and Treatment of Cancer criteria (EORTC) and modified positron emission tomography response criteria in solid tumors (PERCIST) criteria. Results: Administration of PRRT was well tolerated without life-threatening (CTC-4) AEs. CTC-3 hematotoxicity was recorded in 1 patient (16.6%) in group B (thrombocytopenia) and 3 patients (21.4%) in group C (thrombocytopenia in 3, anemia in 1). CTC-3 hepatotoxicity was recorded in 1 patient in group A (8.3%) and C (7.1%), respectively with elevated AST. No nephrotoxicity was observed. When referring to EORTC criteria, the overall disease response rates (DRR) were similar in groups A-C (50.0%, 50.0%, and 42.9%, respectively), and the overall disease control rates (DCR) were higher in group B (83.3%) and C (71.5%) than that in group A (66.7%). When referring to modified PERCIST criteria, lower DRR but similar DCR was found. When selecting comparable baseline SUVmax ranging from 15 to 40, the ΔSUVmax% had slight increase in group A (ΔSUVmax% = 2.1 ± 40.8) but significant decrease in groups B and C (ΔSUVmax% = -38.7 ± 10.0 and -14.7 ± 20.0) after the 1st PRRT (P =0.001), and had decrease in all three groups after the 3rd PRRT (groups A-C, ΔSUVmax%= -6.9 ± 42.3, -49.2 ± 30.9, -11.9 ± 37.9, P = 0.044). Conclusion: Escalated doses of 177Lu-DOTA-EB-TATE up to 3.97 GBq/cycle seem to be well tolerated. 1.89 GBq/cycle and 3.97 GBq/cycle 177Lu-DOTA-EB-TATE were both effective in tumor control and more effective than 1.17 GBq/cycle 177Lu-DOTA-EB-TATE.