title: Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTATATE: the IEO phase I-II study.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst(2)), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of (177)Lu-DOTATATE in multiple cycles.
  
  
  METHODS
  Fifty-one consecutive patients with unresectable/metastatic sst(2)-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 (177)Lu-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  (177)Lu-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.
authors: Division of Nuclear Medicine, European Institute of Oncology, Via Ripamonti, 435-20141 Milan, Italy. lisa.bodei@ieo.it
authors: Lisa
authors: L
authors: Bodei
authors: Marta
authors: M
authors: Cremonesi
authors: Chiara M
authors: CM
authors: Grana
authors: Nicola
authors: N
authors: Fazio
authors: Simona
authors: S
authors: Iodice
authors: Silvia M
authors: SM
authors: Baio
authors: Mirco
authors: M
authors: Bartolomei
authors: Dario
authors: D
authors: Lombardo
authors: Mahila E
authors: ME
authors: Ferrari
authors: Maddalena
authors: M
authors: Sansovini
authors: Marco
authors: M
authors: Chinol
authors: Giovanni
authors: G
authors: Paganelli
mesh_terms: D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000378:metabolism* / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; D017481:Receptors, Somatostatin; C447941:lutetium Lu 177 dotatate; C093733:somatostatin receptor 2; D015282:Octreotide