Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results.
OBJECTIVE
Neuroendocrine tumors over-express somatostatin receptors and literature data have demonstrated the efficacy of the peptide receptor radionuclide therapy with somatostatin analogues labelled with high activities of b-emitting radioisotopes, such as (90)Y and (177)Lu. Yttrium-90 is a pure high energy b-emitter while (177)Lu is a b/g emitter of medium energy. We decided to evaluate an original tandem treatment based on administration of radiolabeled [DOTA(0),Tyr(3)]octreotate (DOTA-TATE) alternating (177)Lu and 90Y. Aim of this study was to evaluate the feasibility, the efficacy and the toxicity of this treatment in neuroendocrine tumors expressing somatostatin receptors relapsed or refractory to conventional therapies.


METHODS
Patients were treated with four therapeutic cycles alternating [(177)Lu]DOTA-TATE (5.55 GBq) and [(90)Y]DOTA-TATE (2.6 GBq). Dosimetric evaluation after administration of [(177)Lu]DOTA-TATE allows to calculate the absorbed doses in healthy organs. Blood samples were collected at 5 min, 1, 6, 24, 48, 72, 96 h and scintigraphy was performed once a day for four days after administration. Toxicity was evaluated considering hematological parameters and renal toxicity was evaluated also by the glomerular filtration rate (GFR). Efficacy related with RECIST criteria.


RESULTS
Up to now 26 patients entered the study and 16 patients completed all cycles. Treatment was well tolerated with no adverse event registered. No damage to healthy organs was revealed in accordance with the calculated absorbed doses. We had a partial response in 10/15 patients evaluated three months after the fourth treatment.


CONCLUSIONS
Up to now only a few patients participated in and concluded this study; preliminary results are encouraging and indicate the feasibility of the study.
Seregni
E
E
Nuclear Medicine, National Cancer Institute, Milan, Italy. ettore.seregni@istitutotumori.mi.it
Maccauro
M
M
Coliva
A
A
Castellani
M R
MR
Bajetta
E
E
Aliberti
G
G
Vellani
C
C
Chiesa
C
C
Martinetti
A
A
Bogni
A
A
Bombardieri
E
E
D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000473:pathology* / Q000532:radiotherapy* / 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*; D011874:Radiometry; D016896:Treatment Outcome
C539274:90Y-octreotate, DOTA(0)-Tyr(3)-Thr(8)-; D009942:Organometallic Compounds; C447941:lutetium Lu 177 dotatate; D015282:Octreotide