Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study.
BACKGROUND
To evaluate the clinical and radiological effectiveness of [DOTA(0), D-Phe(1), Tyr(3)]-octreotate (DOTATATE) Y-90 in patients with extensive progressive gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs).


METHODS
Sixty patients with histologically proven GEP-NETs were treated with DOTATATE Y-90. Clinical responses were assessed 6 weeks after completing therapy and then after each of the 3- to 6-month intervals. The radiological response was classified according to RECIST criteria.


RESULTS
At 6 months after final treatment, radiological partial response (PR; at least a 30% decrease in the sum of the longest diameter of target lesions) was observed in 13 patients (23%), and the remaining patients had stable disease (SD; less than 30% decrease in the sum of the longest diameter of target lesions or less than 20% increase in the sum of the longest diameter of target lesions) (77%). Clinical PR at 6 months was in 43 patients (72%), nine patients had SD and progressive disease (PD) was noted in eight patients. Median progression-free survival (PFS) was 17 months, while the median overall survival (OS) was 22 months. In eight patients with early PD, the PFS was 4.5 and OS 9.5 months, while in those with SD or PR, PFS and OS were 19.5 and 23.5 months, respectively. After 12 months of follow-up, five patients had World Health Organization (WHO) grade 2 or 3 renal toxicity. Haematological toxicity (WHO grade 3 and 4) was noted during therapy in 10% of patients and persisted in 5%.


CONCLUSIONS
DOTATATE Y-90 therapy is effective and relatively safe in patients with GEP-NET. Standard doses of DOTATATE Y-90 result in a relatively low risk of myelotoxicity. However, due to ongoing risk of renal toxicity, careful monitoring of the kidney is recommended.
Cwikla
J B
JB
Department of Radiology and Diagnostic Imaging, Medical Centre for Postgraduate Education and Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw. Electronic address: jaroslaw.cwikla@cskmswia.pl.
Sankowski
A
A
Department of Radiology and Diagnostic Imaging, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw, Poland.
Seklecka
N
N
Department of Radiology and Diagnostic Imaging, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw, Poland.
Buscombe
J R
JR
Department of Nuclear Medicine, Royal Free Hospital, London, UK.
Nasierowska-Guttmejer
A
A
Department of Pathology, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw.
Jeziorski
K G
KG
Department of Radiology and Diagnostic Imaging, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw, Poland; Department of Upper Digestive Tract Cancer, Maria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw.
Mikolajczak
R
R
Institute of Atomic Energy, Radioisotope Centre POLATOM, Otwock-Swierk.
Pawlak
D
D
Institute of Atomic Energy, Radioisotope Centre POLATOM, Otwock-Swierk.
Stepien
K
K
Central Laboratory, Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw.
Walecki
J
J
Department of Radiology and Diagnostic Imaging, Medical Centre for Postgraduate Education and Central Clinical Hospital of Ministry of Internal Affairs and Administration, Warsaw; Department of Experimental Pharmacology, Polish Academy of Science Medical Research Center, Warsaw, Poland.
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D018278:Carcinoma, Neuroendocrine / Q000000981:diagnostic imaging* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015282:Octreotide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D011877:Radionuclide Imaging; D016896:Treatment Outcome; D055815:Young Adult; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*
C539274:90Y-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D015021:Yttrium Radioisotopes; D015282:Octreotide