nach oben

European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

01.10.2014 | Original Article

177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

verfasst von: Giovanni Paganelli, Maddalena Sansovini, Alice Ambrosetti, Stefano Severi, Manuela Monti, Emanuela Scarpi, Caterina Donati, Annarita Ianniello, Federica Matteucci, Dino Amadori

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 10/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We evaluated the activity and safety profile of ¹⁷⁷Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs).

Methods

Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan® completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve.

Results

Twenty-five (58 %) patients were treated with a “standard” Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT.

Conclusion

Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity.

Lawrence B, Gustafsson BI, Chan A, Svejda B, Kidd M, Modlin IM. The epidemiology of gastroenteropancreatic neuroendocrine tumors. Endocrinol Metab Clin North Am. 2011;40(1):1–18. vii.PubMedCrossRef

Öberg K. Management of neuroendocrine tumours. Annals Oncol. 2004;15(4):293–8.

Rinke A, Muller H, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumour growth in patients with metastatic neuroendocrine midgut tumours: a report from the PROMID study group. J Clin Oncol. 2009;27:4656–63.PubMedCrossRef

Kulke MH, Siu LL, Tepper JE, et al. Future directions in the treatment of neuroendocrine tumors: consensus report of the National Cancer Institute Neuroendocrine Tumor clinical trials planning meeting. J Clin Oncol. 2011;29:934–43.PubMedCentralPubMedCrossRef

Steinmuller T, Kianmanesh R, Falconi M, et al. Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: foregut, midgut, hindgut, and unknown primary. Neuroendocrinology. 2008;87:47–62.PubMedCrossRef

Toumpanakis C, Meyer T, Caplin ME. Cytotoxic treatment including embolization/chemoembolization for neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab. 2007;21:131–44.PubMedCrossRef

Paganelli G, Zoboli S, Cremonesi M, et al. Receptor-mediated radiotherapy with 90Y-DOTA-D-Phe1-Tyr3-octreotide. Eur J Nucl Med. 2001;28(4):426–34.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;12:941–5.PubMedCrossRef

Bodei L, Cremonesi M, Grana C, et al. Receptor radionuclide therapy with 90Y-[DOTA]0-Tyr3-octreotide (90Y-DOTATOC) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2004;31:1038–46.PubMedCrossRef

10.

Kwekkeboom DJ, Muller–Brad J, Paganelli G. Overview of results of peptide receptor radionuclide therapy with 3 radiolabeled somatostatin analogs. J Nucl Med. 2005;46 Suppl 1:62S–6S.PubMed

11.

Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treatment with radiolabeled somatostatin analog [177Lu-DOTA0, Tyr3] Ocreotate: toxicity, efficacy and survival. J Clin Oncol. 2008;26:2124–30.PubMedCrossRef

12.

Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabelled somatostatin analogue [90Y-DOTA]-TOC in metastasized neuroendocrine cancers. J Clin Oncol. 2011;29:2416–23.PubMedCrossRef

13.

Klimstra DS, Modlin IR, Coppola D, Lloyd RV, Suster S. The pathologic classification of neuroendocrine tumors: a review of nomenclature, grading, and staging systems. Pancreas. 2010;39(6):707–12.PubMedCrossRef

14.

Cybulla M, Weiner SM, Otte A. End-stage renal disease after treatment with 90Y-DOTATOC. Eur J Nucl Med. 2001;28(10):1552–4.PubMedCrossRef

15.

Piccin A, Grana CM, Negri G, Pusceddu I, Paganelli G, Cortelazzo S. Secondary acute myeloid leukaemia after peptide receptor radionuclide therapy. Ann Hematol. 2012;91(2):299–300.PubMedCrossRef

16.

Bodei L, Cremonesi M, Ferrari M, et al. Long-term evaluation of renal toxicity after peptide receptor radionuclide therapy with 90Y-DOTATOC and 177Lu-DOTATATE: the role of associated risk factors. Eur J Nucl Med Mol Imaging. 2008;35(10):1847–56.PubMedCrossRef

17.

Bosman FT, Carniero F, Hruban RH, et al. WHO classification of tumours of the digestive system. 4th ed. Geneva: World Health Organization; 2010.

18.

Binderup T, Knigge U, Loft A, Federspiel B, Kjaer A. 18 F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors. Clin Cancer Res. 2010;16:978–85.PubMedCrossRef

19.

Breeman WAP, de Blois E, Bakker WH, et al. Radiolabeling DOTA-peptides with 90Yand 177Lu to a high specific activity. In: Chinol M, Paganelli G, editors. Radionuclide peptide cancer therapy. New York, NY: Taylor & Francis Group; 2006. p. 119–26.CrossRef

20.

Green S, Weiss GR. Southwest oncology group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs. 1992;10:239–53.PubMedCrossRef

21.

van Vliet EI, Krenning EP, Teunissen JJ, Bergsma H, Kam BL, Kwekkeboom DJ. Comparison of response evaluation in patients with gastroenteropancreatic and thoracic neuroendocrine tumors after treatment with [177Lu-DOTA0, Tyr3]octreotate. J Nucl Med. 2013;54(10):1689–96.PubMedCrossRef

22.

Common Terminology Criteria for Adverse Events v3.0 (CTCAE, http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf

23.

Kaplan EL, Meier P. Non parametric estimation for incomplete observation. J Am Stat Assoc. 1958;53:457–81.CrossRef

24.

Lawless JS. Statistical models and methods for life-time data. New York, NY: Wiley; 1982.

25.

Bodei L, Cremonesi M, Grana CM, et al. Peptide receptor radionuclide therapy with (177)Lu-DOTATATE: the IEO phase I-II study. Eur J Nucl Med Mol Imaging. 2011;38:2125–35.PubMedCrossRef

26.

Sandström M, Garske-Román U, Granberg D, et al. Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-octreotate treatment. J Nucl Med. 2013;54(1):33–41.PubMedCrossRef

27.

Wessels BW, Konijnenberg MW, Dale RG, et al. MIRD pamphlet No. 20: the effect of model assumptions on kidney dosimetry and response—implications for radionuclide therapy. J Nucl Med. 2008;49:1884–99.PubMedCrossRef

28.

Severi S, Nanni O, Bodei L, et al. Role of (18)FDG PET/CT in patients treated with (177)Lu-DOTATATE for advanced differentiated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40(6):881–8.PubMedCrossRef

29.

Garin E, Le Jeune F, Devillres A, et al. Predictive value of 18 F-FDG PET and somatostatin receptor scintigraphy in patients with metastatic endocrine tumors. J Nucl Med. 2009;50:858–64.PubMedCrossRef

30.

Claringbold PG, Brayshaw PA, Price RA, Turner JH. Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2011;38:302–11.PubMedCrossRef

31.

A Study Comparing Treatment With 177Lu-DOTA0-Tyr3-Octreotate to Octreotide LAR in Patients With Inoperable, Progressive, Somatostatin Receptor Positive Midgut Carcinoid Tumours (NETTER-1). ClinicalTrials.gov Identifier: NCT01578239.

Titel: 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study
verfasst von: Giovanni Paganelli
Maddalena Sansovini
Alice Ambrosetti
Stefano Severi
Manuela Monti
Emanuela Scarpi
Caterina Donati
Annarita Ianniello
Federica Matteucci
Dino Amadori
Publikationsdatum: 01.10.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 10/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-014-2735-5

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 10/2014

Simone Waldt and Klaus Woertler (Eds): Measurements and Classifications in Musculoskeletal Radiology

11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

Mycotic aneurysm of the superior mesenteric artery and other sequelae of prosthetic valve endocarditis on 18F-FDG PET/CT

The combination of FDG PET and dynamic contrast-enhanced MRI improves the prediction of disease-free survival in patients with advanced breast cancer after the first cycle of neoadjuvant chemotherapy

Diagnostic value of FDG-PET/(CT) in children with fever of unknown origin and unexplained fever during immune suppression

The evidence base for the use of internal dosimetry in the clinical practice of molecular radiotherapy