Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II study
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Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst2), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of 177Lu-DOTATATE in multiple cycles.
Fifty-one consecutive patients with unresectable/metastatic sst2-positive tumours, divided into two groups, received escalating activities (3.7–5.18 GBq/cycle, group 1; 5.18–7.4 GBq/cycle, group 2) of 177Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry.
No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8–37 Gy (9–41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival.
177Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles.
Keywords177Lu-DOTATATE Peptide receptor radionuclide therapy Phase I-II PRRT Neuroendocrine tumours
The authors thank Mrs. Deborah Console for the editing of this manuscript.
Conflicts of interest
LB and GP declare one-occasion consultancy with Advanced Accelerator Applications during the preliminary phase of product development of 177Lu-DOTATATE in Italy. All other authors declare that they have no conflicts of interest.
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