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Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 2/2014

01.02.2014 | Original Article

Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

verfasst von: A. Romer, D. Seiler, N. Marincek, P. Brunner, M. T. Koller, Q. K. T. Ng, H. R. Maecke, J. Müller-Brand, C. Rochlitz, M. Briel, C. Schindler, M. A. Walter

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 2/2014

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Abstract

Purpose

Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches.

Methods

In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [90Y-DOTA]-TOC or [177Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups.

Results

Overall, 910 patients underwent 1,804 cycles of [90Y-DOTA]-TOC and 141 patients underwent 259 cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63–1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32).

Conclusion

The present results revealed no difference in median overall survival after [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC.
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Literatur
1.
Zurück zum Zitat Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26(18):3063–72.PubMedCrossRef Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008;26(18):3063–72.PubMedCrossRef
2.
Zurück zum Zitat Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):501–13.PubMedCrossRef Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, et al. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):501–13.PubMedCrossRef
3.
Zurück zum Zitat Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):514–23.PubMedCrossRef Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011;364(6):514–23.PubMedCrossRef
4.
Zurück zum Zitat Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumours. Ann Oncol 2001;12 Suppl 2:S111–4.PubMedCrossRef Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumours. Ann Oncol 2001;12 Suppl 2:S111–4.PubMedCrossRef
5.
Zurück zum Zitat Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24(4):389–427.PubMedCrossRef Reubi JC. Peptide receptors as molecular targets for cancer diagnosis and therapy. Endocr Rev 2003;24(4):389–427.PubMedCrossRef
6.
Zurück zum Zitat Oberg K. Cancer: antitumor effects of octreotide LAR, a somatostatin analog. Nat Rev Endocrinol 2010;6(4):188–9.PubMedCrossRef Oberg K. Cancer: antitumor effects of octreotide LAR, a somatostatin analog. Nat Rev Endocrinol 2010;6(4):188–9.PubMedCrossRef
7.
Zurück zum Zitat Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009;27(28):4656–63.PubMedCrossRef Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 2009;27(28):4656–63.PubMedCrossRef
8.
Zurück zum Zitat Krenning EP, Bakker WH, Breeman WA, Koper JW, Kooij PP, Ausema L, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989;1(8632):242–4.PubMedCrossRef Krenning EP, Bakker WH, Breeman WA, Koper JW, Kooij PP, Ausema L, et al. Localisation of endocrine-related tumours with radioiodinated analogue of somatostatin. Lancet 1989;1(8632):242–4.PubMedCrossRef
9.
Zurück zum Zitat Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 1998;351(9100):417–8.PubMedCrossRef Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet 1998;351(9100):417–8.PubMedCrossRef
10.
Zurück zum Zitat Marincek N, Jörg AC, Brunner P, Schindler C, Koller MT, Rochlitz C, et al. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study. J Transl Med 2013;11:17.PubMedCentralPubMedCrossRef Marincek N, Jörg AC, Brunner P, Schindler C, Koller MT, Rochlitz C, et al. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study. J Transl Med 2013;11:17.PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011;29(17):2416–23.PubMedCrossRef Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol 2011;29(17):2416–23.PubMedCrossRef
12.
Zurück zum Zitat Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, et al. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 1997;24(7):792–5.PubMed Otte A, Jermann E, Behe M, Goetze M, Bucher HC, Roser HW, et al. DOTATOC: a powerful new tool for receptor-mediated radionuclide therapy. Eur J Nucl Med 1997;24(7):792–5.PubMed
13.
Zurück zum Zitat Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 2012;30(10):1100–6.PubMedCrossRef Villard L, Romer A, Marincek N, Brunner P, Koller MT, Schindler C, et al. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers. J Clin Oncol 2012;30(10):1100–6.PubMedCrossRef
14.
Zurück zum Zitat Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26(11):1439–47.PubMedCrossRef Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, et al. Yttrium-90 DOTATOC: first clinical results. Eur J Nucl Med 1999;26(11):1439–47.PubMedCrossRef
15.
Zurück zum Zitat Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12(7):941–5.PubMedCrossRef Waldherr C, Pless M, Maecke HR, Haldemann A, Mueller-Brand J. The clinical value of [90Y-DOTA]-D-Phe1-Tyr3-octreotide (90Y-DOTATOC) in the treatment of neuroendocrine tumours: a clinical phase II study. Ann Oncol 2001;12(7):941–5.PubMedCrossRef
16.
Zurück zum Zitat Iten F, Müller B, Schindler C, Rochlitz C, Oertli D, Mäcke HR, et al. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res 2007;13(22 Pt 1):6696–702.PubMedCrossRef Iten F, Müller B, Schindler C, Rochlitz C, Oertli D, Mäcke HR, et al. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res 2007;13(22 Pt 1):6696–702.PubMedCrossRef
17.
Zurück zum Zitat Iten F, Muller B, Schindler C, Rasch H, Rochlitz C, Oertli D, et al. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer 2009;115(10):2052–62.PubMedCrossRef Iten F, Muller B, Schindler C, Rasch H, Rochlitz C, Oertli D, et al. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer 2009;115(10):2052–62.PubMedCrossRef
18.
Zurück zum Zitat Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med 1994;330(13):877–84.PubMedCrossRef Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med 1994;330(13):877–84.PubMedCrossRef
19.
Zurück zum Zitat de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:13S–7S.PubMed de Jong M, Breeman WA, Valkema R, Bernard BF, Krenning EP. Combination radionuclide therapy using 177Lu- and 90Y-labeled somatostatin analogs. J Nucl Med 2005;46 Suppl 1:13S–7S.PubMed
20.
Zurück zum Zitat Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med 2007;26(11):2389–430.PubMedCrossRef Putter H, Fiocco M, Geskus RB. Tutorial in biostatistics: competing risks and multi-state models. Stat Med 2007;26(11):2389–430.PubMedCrossRef
21.
Zurück zum Zitat Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496–509.CrossRef Fine JP, Gray RJ. A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 1999;94:496–509.CrossRef
22.
Zurück zum Zitat Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92(3):205–16.PubMedCrossRef Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000;92(3):205–16.PubMedCrossRef
23.
Zurück zum Zitat Siegel JA, Stabin MG. Absorbed fractions for electrons and beta particles in spheres of various sizes. J Nucl Med 1994;35(1):152–6.PubMed Siegel JA, Stabin MG. Absorbed fractions for electrons and beta particles in spheres of various sizes. J Nucl Med 1994;35(1):152–6.PubMed
24.
Zurück zum Zitat Sun X, Briel M, Walter SD, Guyatt GH. Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 2010;340:c117. Sun X, Briel M, Walter SD, Guyatt GH. Is a subgroup effect believable? Updating criteria to evaluate the credibility of subgroup analyses. BMJ 2010;340:c117.
25.
Zurück zum Zitat Walrand S, Barone R, Pauwels S, Jamar F. Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts. Eur J Nucl Med Mol Imaging 2011;38(7):1270–80.PubMedCrossRef Walrand S, Barone R, Pauwels S, Jamar F. Experimental facts supporting a red marrow uptake due to radiometal transchelation in 90Y-DOTATOC therapy and relationship to the decrease of platelet counts. Eur J Nucl Med Mol Imaging 2011;38(7):1270–80.PubMedCrossRef
26.
Zurück zum Zitat Chen PS, Terepka AR, Hodge HC. The pharmacology and toxicology of the bone seekers. Annu Rev Pharmacol 1961;1(1):369–96.CrossRef Chen PS, Terepka AR, Hodge HC. The pharmacology and toxicology of the bone seekers. Annu Rev Pharmacol 1961;1(1):369–96.CrossRef
27.
Zurück zum Zitat Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26(13):2124–30.PubMedCrossRef Kwekkeboom DJ, de Herder WW, Kam BL, van Eijck CH, van Essen M, Kooij PP, et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008;26(13):2124–30.PubMedCrossRef
Metadaten
Titel
Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours
verfasst von
A. Romer
D. Seiler
N. Marincek
P. Brunner
M. T. Koller
Q. K. T. Ng
H. R. Maecke
J. Müller-Brand
C. Rochlitz
M. Briel
C. Schindler
M. A. Walter
Publikationsdatum
01.02.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 2/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-013-2559-8

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