title: Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [177Lu-DOTA(0),Tyr3]octreotate.
abstract: Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [(90)Y-DOTA(0),Tyr(3)]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA(0),Tyr(3)]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA(0),Tyr(3)]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide (177)Lu, it has proved very successful in achieving tumour regression in animal models. The effects of (177)Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi (177)Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours. However, in view of the high success rate of therapy with (177)Lu-octreotate and the absence of serious side-effects, we advocate its use in patients with GEP tumours without waiting for tumour progression.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands. kwekkeboom@nuge.azr.nl
authors.forename: D J
authors.initials: DJ
authors.lastname: Kwekkeboom
authors.forename: W H
authors.initials: WH
authors.lastname: Bakker
authors.forename: B L
authors.initials: BL
authors.lastname: Kam
authors.forename: J J M
authors.initials: JJ
authors.lastname: Teunissen
authors.forename: P P M
authors.initials: PP
authors.lastname: Kooij
authors.forename: W W
authors.initials: WW
authors.lastname: de Herder
authors.forename: R A
authors.initials: RA
authors.lastname: Feelders
authors.forename: C H J
authors.initials: CH
authors.lastname: van Eijck
authors.forename: M
authors.initials: M
authors.lastname: de Jong
authors.forename: A
authors.initials: A
authors.lastname: Srinivasan
authors.forename: J L
authors.initials: JL
authors.lastname: Erion
authors.forename: E P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D015746:Abdominal Pain / Q000209:etiology; D000328:Adult; D000368:Aged; D000505:Alopecia / Q000209:etiology; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D018358:Neuroendocrine Tumors / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary*; D015282:Octreotide / Q000031:analogs & derivatives; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary*; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C447941:lutetium Lu 177 dotatate; D015282:Octreotide