High clinical and morphologic response using90Y-DOTA-octreotate sequenced with177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.
OBJECTIVE
Bulky disease is an adverse prognostic factor for177Lu-DOTA-octreotate (177Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT).90Y-DOTA-octreotate (90Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than177Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially.


METHODS
We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of90Y-DOTATATE followed by 2-3 cycles of177Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival.


RESULTS
Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq90Y-DOTATATE, and 21 GBq177Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months.


CONCLUSIONS
PRCRT with90Y -DOTATATE followed by177Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved treatments, particularly given the adverse prognostic features of this cohort.
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Grace.kong@petermac.org.
Grace
http://orcid.org/0000-0002-0834-6888
G
Kong
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Jason
J
Callahan
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|Department of Medicine, The University of Melbourne, Parkville, Australia.
Michael S
MS
Hofman
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
David A
DA
Pattison
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Tim
T
Akhurst
Division of Cancer Medicine, Neuroendocrine Tumour Unit, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.|The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia.
Michael
M
Michael
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Peter
P
Eu
Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. Rod.hicks@petermac.org.|The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Australia. Rod.hicks@petermac.org.
Rodney J
RJ
Hicks
D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008231:Lymphopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / 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; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013921:Thrombocytopenia / Q000209:etiology
C539274:90Y-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C447941:lutetium Lu 177 dotatate; D015282:Octreotide
Lutetium; Neuroendocrine; Octreotate; Peptide receptors; Radionuclide therapy; Yttrium
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