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Clinical Trial
. 2016 Feb 13;6(4):501-10.
doi: 10.7150/thno.13702. eCollection 2016.

[(177)Lu-DOTA](0)-D-Phe(1)-Tyr(3)-Octreotide ((177)Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

Richard P Baum  1 , Andreas W Kluge  2 , Harshad Kulkarni  1 , Ulrike Schorr-Neufing  2 , Karin Niepsch  1 , Norman Bitterlich  2 , Cees J A van Echteld  2
Affiliations
Clinical Trial

[(177)Lu-DOTA](0)-D-Phe(1)-Tyr(3)-Octreotide ((177)Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

Richard P Baum et al. Theranostics. .

Abstract

Purpose: To characterise efficacy and safety of (177)Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET).

Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with (177)Lu-DOTATOC were analysed retrospectively. Subjects were administered (177)Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin.

Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment.

Conclusion: (177)Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with impaired bone marrow or renal function, which reflects a uniquely low uptake of (177)Lu-DOTATOC by normal organs.

Keywords: Neuroendocrine tumour; peptide receptor; radionuclide therapy; radiotherapy; somatostatin analogue.; somatostatin receptor.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Kaplan-Meier estimates of PFS in the study population depending on number of 177Lu-DOTATOC PRRT cycles,
Figure 2
Figure 2
Kaplan-Meier estimates of OS in the study population depending on number of 177Lu-DOTATOC PRRT cycles.
Figure 3
Figure 3
Time of first disease control and best response after start of PRRT in 37 responding patients.
Figure 4
Figure 4
Kaplan-Meier estimates of PFS in patients who received >1 cycle with or without prior medical therapy.
Figure 5
Figure 5
Change of TER relative to baseline in relation to the median time after the first 177Lu-DOTATOC PRRT cycle.
Figure 6
Figure 6
Change of GFR relative to baseline in relation to the median time after the first 177Lu-DOTATOC PRRT cycle.
See this image and copyright information in PMC

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