title: Safety of multiple repeated cycles of177Lu-octreotate in patients with recurrent neuroendocrine tumour.
abstract: OBJECTIVE
  Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of177Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET.
  
  
  METHODS
  We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles.
  
  
  RESULTS
  We observed no life-threatening adverse events (CTC-4) during177Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001).
  
  
  CONCLUSIONS
  Therapy with eight or more cycles of177Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET.
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Yordanova
authors.affiliation: Department of Internal Medicine 3, University Hospital Bonn, Bonn, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Mayer
authors.affiliation: Department of Internal Medicine 3, University Hospital Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Department of Internal Medicine 1, University Hospital Bonn, Bonn, Germany.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gonzalez-Carmona
authors.affiliation: Department of Internal Medicine 1, University Hospital Bonn, Bonn, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Strassburg
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Essler
authors.affiliation: Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany. hojjat.ahmadzadehfar@ukbonn.de.
authors.forename: Hojjat
authors.initials: H
authors.lastname: Ahmadzadehfar
mesh_terms: D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000378:metabolism / Q000628:therapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018000:Receptors, Peptide / Q000378:metabolism; D012008:Recurrence; D012189:Retrospective Studies; D012449:Safety; D016019:Survival Analysis
chemical_list: C554548:177Lu-octreotate; D018000:Receptors, Peptide; D015282:Octreotide
keywords: 177Lu-octreotate; Neuroendocrine tumours; PRRT; Relapse therapy