Skip to main content
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging 7/2014

01.07.2014 | Original Article

177Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years’ experience from a tertiary cancer care centre in India

verfasst von: Madhav Danthala, K. G. Kallur, G. R. Prashant, K. Rajkumar, M. Raghavendra Rao

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 7/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with 177Lu-DOTATATE (177Lu-[DOTA0,Tyr3] octreotate) is a promising new option in the treatment of metastatic NETs.

Methods

Patients with metastatic NET who underwent 177Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a 68Ga-DOTANOC PET/CT scan and a posttherapy 177Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done.

Results

Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of 177Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of 177Lu-DOTATATE (log-rank Mantel-Cox Χ 2 = 8.01, p = 0.005).

Conclusion

Our study showed that treatment with 177Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of 177Lu-DOTATATE are given, with careful monitoring for possible side effects.
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;26:3063–72.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;26:3063–72.PubMedCrossRef
2.
Zurück zum Zitat Oberg K, Castellano D. Current knowledge on diagnosis and staging of neuroendocrine tumors. Cancer Metastasis Rev. 2011;30 Suppl 1:3–7.PubMedCrossRef Oberg K, Castellano D. Current knowledge on diagnosis and staging of neuroendocrine tumors. Cancer Metastasis Rev. 2011;30 Suppl 1:3–7.PubMedCrossRef
3.
Zurück zum Zitat De Herder WW, Hofland LJ, Van der Lely AJ, Lamberts SWJ. Somatostatin receptors in gastro-entero-pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2003;10(4):451–8.PubMedCrossRef De Herder WW, Hofland LJ, Van der Lely AJ, Lamberts SWJ. Somatostatin receptors in gastro-entero-pancreatic neuroendocrine tumours. Endocr Relat Cancer. 2003;10(4):451–8.PubMedCrossRef
4.
Zurück zum Zitat De Jong M, Breeman WA, Kwekkeboom DJ, Valkema R, Krenning EP. Tumor imaging and therapy using radiolabeled somatostatin analogues. Acc Chem Res. 2009;42(7):873–80.PubMedCrossRef De Jong M, Breeman WA, Kwekkeboom DJ, Valkema R, Krenning EP. Tumor imaging and therapy using radiolabeled somatostatin analogues. Acc Chem Res. 2009;42(7):873–80.PubMedCrossRef
5.
Zurück zum Zitat Sward C, Bernhardt P, Johanson V, Schmitt A, Ahlman H, Stridsberg M, et al. Comparison of [177Lu-DOTA0, Tyr3]-octreotate and [177Lu-DOTA0, Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1. Cancer Biother Radiopharm. 2008;23(1):114–20.PubMedCrossRef Sward C, Bernhardt P, Johanson V, Schmitt A, Ahlman H, Stridsberg M, et al. Comparison of [177Lu-DOTA0, Tyr3]-octreotate and [177Lu-DOTA0, Tyr3]-octreotide for receptor-mediated radiation therapy of the xenografted human midgut carcinoid tumor GOT1. Cancer Biother Radiopharm. 2008;23(1):114–20.PubMedCrossRef
6.
Zurück zum Zitat Wehrmann C, Senftleben S, Zachert C, Muller D, Baum RP. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm. 2007;22(3):406–16.PubMedCrossRef Wehrmann C, Senftleben S, Zachert C, Muller D, Baum RP. Results of individual patient dosimetry in peptide receptor radionuclide therapy with 177Lu DOTA-TATE and 177Lu DOTA-NOC. Cancer Biother Radiopharm. 2007;22(3):406–16.PubMedCrossRef
7.
Zurück zum Zitat Frilling A, Weber F, Saner F, Bockisch A, Hofmann M, Mueller-Brand J, et al. Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors. Surgery. 2006;140(6):968–76.PubMedCrossRef Frilling A, Weber F, Saner F, Bockisch A, Hofmann M, Mueller-Brand J, et al. Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors. Surgery. 2006;140(6):968–76.PubMedCrossRef
8.
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 [177Lu-DOTA0, 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 [177Lu-DOTA0, Tyr3] octreotate: toxicity, efficacy, and survival. J Clin Oncol. 2008;26(13):2124–30.PubMedCrossRef
9.
Zurück zum Zitat Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTAOTyr3] octreotate: comparison with [111In-DTPAo] octreotide in patients. Eur J Nucl Med. 2001;28(9):1319–25.PubMedCrossRef Kwekkeboom DJ, Bakker WH, Kooij PP, Konijnenberg MW, Srinivasan A, Erion JL, et al. [177Lu-DOTAOTyr3] octreotate: comparison with [111In-DTPAo] octreotide in patients. Eur J Nucl Med. 2001;28(9):1319–25.PubMedCrossRef
10.
Zurück zum Zitat Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, et al. Comparison of [(177)Lu-DOTA(0), Tyr(3)] octreotate and [(177)Lu-DOTA(0), Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006;33(11):1346–51.PubMedCrossRef Esser JP, Krenning EP, Teunissen JJ, Kooij PP, van Gameren AL, Bakker WH, et al. Comparison of [(177)Lu-DOTA(0), Tyr(3)] octreotate and [(177)Lu-DOTA(0), Tyr(3)]octreotide: which peptide is preferable for PRRT? Eur J Nucl Med Mol Imaging. 2006;33(11):1346–51.PubMedCrossRef
11.
Zurück zum Zitat Zaknun JJ, Bodei L, Mueller-Brand J, Pavel ME, Baum RP, Hörsch D, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40:800–16.PubMedCentralPubMedCrossRef Zaknun JJ, Bodei L, Mueller-Brand J, Pavel ME, Baum RP, Hörsch D, et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2013;40:800–16.PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I–II study. Eur J Nucl Med Mol Imaging. 2011;38(12):2125–35.PubMedCrossRef Bodei L, Cremonesi M, Grana CM, Fazio N, Iodice S, Baio SM, et al. Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I–II study. Eur J Nucl Med Mol Imaging. 2011;38(12):2125–35.PubMedCrossRef
13.
Zurück zum Zitat Garkavij M, Nickel M, Sjogreen-Gleisner K, Ljungberg M, Ohlsson T, Wingardh K, et al. 177Lu-[DOTA0, Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer. 2010;116 Suppl 4:1084–92.PubMedCrossRef Garkavij M, Nickel M, Sjogreen-Gleisner K, Ljungberg M, Ohlsson T, Wingardh K, et al. 177Lu-[DOTA0, Tyr3] octreotate therapy in patients with disseminated neuroendocrine tumors: analysis of dosimetry with impact on future therapeutic strategy. Cancer. 2010;116 Suppl 4:1084–92.PubMedCrossRef
14.
Zurück zum Zitat Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. In: Baum RP, Rösch F, editors. Theranostics, gallium-68, and other radionuclides. Berlin: Springer; 2013. p. 457–65.CrossRef Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Krause BJ, et al. Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry. In: Baum RP, Rösch F, editors. Theranostics, gallium-68, and other radionuclides. Berlin: Springer; 2013. p. 457–65.CrossRef
15.
Zurück zum Zitat Kunikowska J, Królicki L, Sowa-Staszczak A, Hubalewska-Dydejczyk A, Pawlak D, Mikolajczak R, et al. Polish experience in peptide receptor radionuclide therapy. In: Baum RP, Rösch F, editors. Theranostics, gallium-68, and other radionuclides. Berlin: Springer; 2013. p. 467–78.CrossRef Kunikowska J, Królicki L, Sowa-Staszczak A, Hubalewska-Dydejczyk A, Pawlak D, Mikolajczak R, et al. Polish experience in peptide receptor radionuclide therapy. In: Baum RP, Rösch F, editors. Theranostics, gallium-68, and other radionuclides. Berlin: Springer; 2013. p. 467–78.CrossRef
16.
Zurück zum Zitat Teunissen JJ, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0, Tyr3] octreotate. J Clin Oncol. 2004;22(13):2724–9.PubMedCrossRef Teunissen JJ, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0, Tyr3] octreotate. J Clin Oncol. 2004;22(13):2724–9.PubMedCrossRef
17.
Zurück zum Zitat de Jong M, Krenning EP. New advances in peptide receptor radionuclide therapy. J Nucl Med. 2002;43:617–20.PubMed de Jong M, Krenning EP. New advances in peptide receptor radionuclide therapy. J Nucl Med. 2002;43:617–20.PubMed
18.
Zurück zum Zitat Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. (86YDOTA0)-DPhe1-Tyr3-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging. 2003;30:510–8.PubMedCrossRef Jamar F, Barone R, Mathieu I, Walrand S, Labar D, Carlier P, et al. (86YDOTA0)-DPhe1-Tyr3-octreotide (SMT487) – a phase 1 clinical study: pharmacokinetics, biodistribution and renal protective effect of different regimens of amino acid co-infusion. Eur J Nucl Med Mol Imaging. 2003;30:510–8.PubMedCrossRef
19.
Zurück zum Zitat Irina R, Robert R, Walter K, Rosemany D, Wendy G. Hepatic artery embolization with combined 131-I-lipiodol and doxorubicin/cisplatin as local radiosensitizers for the treatment of neuroendocrine tumour (NET) liver metastases. J Nucl Med. 2006;47 Suppl 1:105P. Irina R, Robert R, Walter K, Rosemany D, Wendy G. Hepatic artery embolization with combined 131-I-lipiodol and doxorubicin/cisplatin as local radiosensitizers for the treatment of neuroendocrine tumour (NET) liver metastases. J Nucl Med. 2006;47 Suppl 1:105P.
20.
Zurück zum Zitat Natasha S, Krishna BA, Madhusudhan V, Meera V, Sharmila B, Tapas D, et al. Lutetium DOTATATE whole body scans: a novel approach for evaluation of neuroendocrine tumours. Indian J Nucl Med. 2011;26(3):135–8.CrossRef Natasha S, Krishna BA, Madhusudhan V, Meera V, Sharmila B, Tapas D, et al. Lutetium DOTATATE whole body scans: a novel approach for evaluation of neuroendocrine tumours. Indian J Nucl Med. 2011;26(3):135–8.CrossRef
21.
Zurück zum Zitat Sowa-Staszczak A, Pach D, Chrzan R, Trofimiuk M, Stefańska A, Tomaszuk M, et al. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging. 2011;38(9):1669–74.PubMedCentralPubMedCrossRef Sowa-Staszczak A, Pach D, Chrzan R, Trofimiuk M, Stefańska A, Tomaszuk M, et al. Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs). Eur J Nucl Med Mol Imaging. 2011;38(9):1669–74.PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat van Essen M, Krenning EP, Kam BL, de Herder WW, Feelders RA, Kwekkeboom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010;51(3):383–90.PubMedCrossRef van Essen M, Krenning EP, Kam BL, de Herder WW, Feelders RA, Kwekkeboom DJ. Salvage therapy with (177)Lu-octreotate in patients with bronchial and gastroenteropancreatic neuroendocrine tumors. J Nucl Med. 2010;51(3):383–90.PubMedCrossRef
23.
Zurück zum Zitat Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–12.PubMedCrossRef Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378(9808):2005–12.PubMedCrossRef
24.
Zurück zum Zitat Gupta S, Yao JC, Ahrar K, Wallace MJ, Morello FA, Madoff DC, et al. Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J. 2003;9:261–7.PubMedCrossRef Gupta S, Yao JC, Ahrar K, Wallace MJ, Morello FA, Madoff DC, et al. Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience. Cancer J. 2003;9:261–7.PubMedCrossRef
25.
Zurück zum Zitat Hajarizadeh H, Ivancev K, Mueller CR, Fletcher WS, Woltering EA. Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate. Am J Surg. 1992;163:479–83.PubMedCrossRef Hajarizadeh H, Ivancev K, Mueller CR, Fletcher WS, Woltering EA. Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate. Am J Surg. 1992;163:479–83.PubMedCrossRef
26.
Zurück zum Zitat Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ, Madoff DC, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors. Cancer. 2005;104(8):1590–602.PubMedCrossRef Gupta S, Johnson MM, Murthy R, Ahrar K, Wallace MJ, Madoff DC, et al. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors. Cancer. 2005;104(8):1590–602.PubMedCrossRef
27.
Zurück zum Zitat Seregni E, Maccauro M, Coliva A, Castellani MR, Bajetta E, Aliberti G, et al. Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results. Q J Nucl Med Mol Imaging. 2010;54(1):84–91.PubMed Seregni E, Maccauro M, Coliva A, Castellani MR, Bajetta E, Aliberti G, et al. Treatment with tandem [(90)Y]DOTA-TATE and [(177)Lu] DOTA-TATE of neuroendocrine tumors refractory to conventional therapy: preliminary results. Q J Nucl Med Mol Imaging. 2010;54(1):84–91.PubMed
28.
Zurück zum Zitat Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, Mikołajczak R, Sowa-Staszczak A, Pawlak D. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38(10):1788–97.PubMedCentralPubMedCrossRef Kunikowska J, Królicki L, Hubalewska-Dydejczyk A, Mikołajczak R, Sowa-Staszczak A, Pawlak D. Clinical results of radionuclide therapy of neuroendocrine tumours with 90Y-DOTATATE and tandem 90Y/177Lu-DOTATATE: which is a better therapy option? Eur J Nucl Med Mol Imaging. 2011;38(10):1788–97.PubMedCentralPubMedCrossRef
Metadaten
Titel
177Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years’ experience from a tertiary cancer care centre in India
verfasst von
Madhav Danthala
K. G. Kallur
G. R. Prashant
K. Rajkumar
M. Raghavendra Rao
Publikationsdatum
01.07.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 7/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-014-2710-1

Weitere Artikel der Ausgabe 7/2014

European Journal of Nuclear Medicine and Molecular Imaging 7/2014 Zur Ausgabe