title: Myelotoxicity of Peptide Receptor Radionuclide Therapy of Neuroendocrine Tumors: A Decade of Experience.
abstract: OBJECTIVE
  This review of the literature, and the authors' own decade of experience with lutetium-177-octreotate-capecitabine±temozolomide peptide receptor radionuclide therapy (PRRT)-chemotherapy of GEPNETs, analyses the risk of both short- and long-term hematotoxicity.
  
  
  BACKGROUND
  Myelodysplastic syndrome (MDS) and acute leukemia (AL) have been associated with PRRT in heavily pretreated patients with a history of exposure to alkylating agents. Commenced 15 years ago, PRRT is now becoming established as first- and second-line therapy for gastroentero pancreatic neuroendocrine tumors (GEPNETs), and early treatment minimizes myelotoxicity, which is the most significant potential adverse event following PRRT.
  
  
  RESULTS
  Sixteen key articles involving primary research were identified. A total of 2225 patients were treated (2104 treated with PRRT monotherapy and 121 with PRRT combined with chemotherapy). The average age of patients in these studies ranged from 53 to 64 years with median duration of follow-up ranging from 6 to 62 months. Short-term myelotoxicity was observed in 221 patients (10%), occurring in 213 of 2104 patients treated with PRRT monotherapy and 8 of 121 patients treated with PRRT combined with chemotherapy. Acute toxicity manifested as modest self-limited grade 3/4 toxicity (CTCAE or WHO), most often affecting platelets during the first cycle of treatment. Toxicity manifesting early was easily managed with dose modification or therapy cessation and was ameliorated by appropriate patient selection. MDS/AL was a rare stochastic event occurring in 32 (1.4%) patients. Where bone marrow biopsy was performed, cases of MDS displayed cytogenetic abnormalities, consistent with secondary MDS. Factors associated with myelotoxicity included age >70 years, impaired renal function, baseline cytopenias, prior number of therapies, prior chemotherapy (alkylating agents), and prior radiotherapy.
  
  
  CONCLUSIONS
  Early therapy with PRRT-containing regimens improves outcomes, minimizes myelotoxicity, and renders the risk of MDS and AL negligible.
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia , Crawley, Australia .
authors.forename: Murali
authors.initials: M
authors.lastname: Kesavan
authors.affiliation: School of Medicine and Pharmacology, The University of Western Australia , Crawley, Australia .
authors.forename: J Harvey
authors.initials: JH
authors.lastname: Turner
mesh_terms: D000069287:Capecitabine / Q000009:adverse effects / Q000627:therapeutic use; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008187:Lutetium / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000209:etiology*; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D011832:Radiation Injuries / Q000209:etiology*; D011868:Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects*; D000077204:Temozolomide
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D000069287:Capecitabine; D003606:Dacarbazine; D015282:Octreotide; D000077204:Temozolomide
keywords: Lu-177; cancer; myelosuppression; radionuclide therapy; radiosensitizers