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
- 10.Breeman WAP, de Blois E, Bakker WH, Krenning EP. Radiolabeling DOTA-peptides with 90Y and 177Lu to a high specific activity. In: Chinol M, Paganelli G, editors. Radionuclide peptide cancer therapy. New York: Taylor & Francis Group; 2006. p. 119–26.Google Scholar
- 15.Common Terminology Criteria for Adverse Events v3.0 (CTCAE, http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf
- 20.Bodei L, Cremonesi M, Ferrari M, Pacifici M, Grana CM, Bartolomei M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging 2008;35(10):1847–56.PubMedGoogle Scholar
- 23.Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study of the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID study group. J Clin Oncol 2009;27(28):4656–63.PubMedGoogle Scholar
- 26.Davì MV, Bodei L, Ferdeghini M, Falconi M, Testoni M, Paganelli G, et al. Multidisciplinary approach including receptor radionuclide therapy with 90Y-DOTATOC ([90Y-DOTA0, Tyr3]-octreotide) and 177Lu-DOTATATE ([177Lu-DOTA0, Tyr3]-octreotate) in ectopic Cushing syndrome from a metastatic gastrinoma: a promising proposal. Endocr Pract 2008;14(2):213–8.PubMedGoogle Scholar