Abstract
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Objectives: The aim of this dose escalation study is to evaluate the safety and efficacy of 177Lu-DOTA-EB-TATE, a novel radiolabeled somatostatin analogue modified by Evans Blue to prolong circulation half-life and increase tumor accumulation, in treatment of patients with metastatic neuroendocrine tumors (NET).
Methods: With institute review board approval, 26 patients with metastatic NET were prospectively enrolled into three groups: Group A (n = 6) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTATATE as controls; Group B (n = 6) administered approximately 1.85 GBq (50 mCi) 177Lu-DOTA-EB-TATE; Group C (n = 14) administered approximately 3.7 GBq (100 mCi) 177Lu-DOTA-EB-TATE. Complete blood count, liver function and kidney function were tested at baseline, 1 week and 4 weeks for safety evaluation. 68Ga-DOTATATE PET/CT were performed at baseline and 2-3 months after treatment for response evaluation. Maximum standardized uptake values (SUVmax) of the tumors ≥2.0 cm in diameter but no more than 5 lesions in each patient were measured. Percentage of change of SUVmax after treatment (Δ%) were calculated.
Results: According to Common Toxicity Criteria (CTC), one patient in group A died of progressive disease within 4 weeks, whereas the other 5 patients had no report of hematotoxicity, nephrotoxicity or hepatotoxicity. In group B, only one of the six patients was recorded with CTC-2 hematotoxicity. In group C with 14 patients, CTC-1 and CTC-3 hematotoxicity was recorded in 1 and 2 patients, respectively; CTC-1 hepatotoxicity occurred in 3 patients. The baseline SUVmax in group A, B and C were 29.3±13.0, 41.4±51.9 and 29.6±19.5 respectively (P>0.05). After one-cycle treatment, the SUVmax decreased in group B (Δ%=-17.4%±29.3%) and group C (Δ%=-15.1%±39.1%), but mildly increased in general in group A (Δ%=5.4%±45.9%) (P>0.05). There was a negative correlation between the baseline SUVmax and post-treatment ΔSUVmax in group B and C (r=0.95 and -0.86, respectively, P<0.001). Referring to the PERSIST criteria, 16.7% (1/6), 50% (3/6) and 50% (7/14) were evaluated as partial response in groups A, B and C, respectively. When selecting lesions with comparable baseline SUVmax ranging from 20 to 40, the baseline SUVmax were 30.6±5.8, 29.1±5.1 and 30.5± 6.2 respectively in groups A, B and C (P>0.05). Consistent with the previous results, SUVmax significantly decreased in group B (Δ%=-10.6% ±4.2%) and group C (Δ%=-5.7 ± 5.2%), but mildly increased in general in group A (Δ%=5.3% ±13.4%) (P<0.05).
Conclusions: One cycle of treatmentusing 1.85 GBq (50 mCi) or 3.7GBq (100 mCi) 177Lu-DOTA-EB-TATE seems to be well tolerated and more effective than that of 3.7 GBq (100 mCi) 177Lu-DOTATATE. This preliminary result merits further investigation using more cycles of 177Lu-DOTA-EB-TATE treatment.
Changes between baseline and 4 weeks after treatment