title: 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide.
abstract: OBJECTIVE
  The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity (111)In-pentetreotide can be safely treated with (177)Lu-octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent.
  
  
  METHODS
  Records of 27 patients (aged 17-75) who received 69 (median 3 per patient) (177)Lu-octreotate administrations, including 29 in conjunction with radiosensitising infusional 5-fluorouracil (5-FU) (n = 27), or capecitabine (n = 2), between October 2005 and July 2007 subsequent to 1-8 prior cycles of (111)In-pentetreotide therapy were analysed. Toxicity was assessed during and at 8-12 weeks post-treatment, with further long-term assessments including survival status reviewed till death or study close-out date of 1 November 2009.
  
  
  RESULTS
  Reduction in blood counts was most marked following the first dose of (177)Lu-octreotate but at early follow-up the only major haematological toxicity was a single case of grade 4 lymphopaenia. Both the presence of bone metastases and the administration of chemotherapy tended to result in greater reduction in blood counts, but these differences did not reach statistical significance. On long-term follow-up, 16 patients (59%) are alive with median overall survival of 36 months (32-44 months from first (177)Lu-octreotate therapy). None of the recorded deaths was directly related to treatment toxicity. One patient had late grade 4 anaemia and thrombocytopaenia secondary to bone marrow failure from progressive infiltration by tumour. No other significant long-term haematological toxicities were recorded and no leukaemia was observed. No renal toxicity was observed on serial serum creatinine or radionuclide glomerular filtration rate (GFR) determination on initial or long-term follow-up.
  
  
  CONCLUSIONS
  (177)Lu-octreotate is a safe and well-tolerated therapy for patients who have previously been treated with (111)In-pentetreotide and can be safely combined with radiosensitising chemotherapy. However, caution is recommended in patients with bone metastases. Significant late toxicities including bone marrow or renal failure, or leukaemia directly related to radionuclide therapy, did not occur in our series.
authors.affiliation: Centre for Molecular Imaging, Peter MacCallum Cancer Centre, 12 St Andrew's Place, East Melbourne, VIC 3002, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Hubble
authors.forename: Grace
authors.initials: G
authors.lastname: Kong
authors.forename: Michael
authors.initials: M
authors.lastname: Michael
authors.forename: Val
authors.initials: V
authors.lastname: Johnson
authors.forename: Shakher
authors.initials: S
authors.lastname: Ramdave
authors.forename: Rodney John
authors.initials: RJ
authors.lastname: Hicks
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005500:Follow-Up Studies; D006403:Hematologic Tests; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000097:blood / Q000378:metabolism / Q000628:therapy*; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018000:Receptors, Peptide / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D055815:Young Adult
chemical_list: C554548:177Lu-octreotate; D009942:Organometallic Compounds; D011355:Prodrugs; D011838:Radiation-Sensitizing Agents; D018000:Receptors, Peptide; C094279:indium-111-octreotide; D003841:Deoxycytidine; D000069287:Capecitabine; D015282:Octreotide; D005472:Fluorouracil
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