This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kwekkeboom, D. J. Articles by Krenning, E. P. Search for Related Content PubMed PubMed Citation Articles by Kwekkeboom, D. J. Articles by Krenning, E. P. Social Bookmarking                            What's this?

Radiolabeled Somatostatin Analog [¹⁷⁷Lu-DOTA⁰,Tyr³]Octreotate in Patients With Endocrine Gastroenteropancreatic Tumors

From the Departments of Nuclear Medicine, Internal Medicine, and Surgery, Erasmus Medical Center, Rotterdam, the Netherlands

Address reprint requests to D.J. Kwekkeboom, MD, Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands; e-mail: d.j.kwekkeboom{at}erasmusmc.nl

PURPOSE: There are few treatment options for patients with metastasized or inoperable endocrine gastroenteropancreatic (GEP) tumors. Chemotherapy can be effective, but the response is usually less than 1 year. Here, we present the results of treatment with a radiolabeled somatostatin analog, [¹⁷⁷Lu-DOTA⁰,Tyr³]octreotate (¹⁷⁷Lu-octreotate).

PATIENTS AND METHODS: One hundred thirty-one patients with somatostatin receptor-positive tumors were treated with up to a cumulative dose of 600 to 800 mCi (22.2 to 29.6 GBq) of ¹⁷⁷Lu-octreotate.

RESULTS: One patient developed renal insufficiency, and another patient developed hepatorenal syndrome. Creatinine clearance did not change significantly in the other patients. WHO hematologic toxicity grade 3 or 4 occurred after less than 2% of the administrations. We observed complete remission in three patients (2%), partial remission in 32 patients (26%), minor response (tumor diameter decrease of 25% to 50%) in 24 patients (19%), stable disease (SD) in 44 patients (35%), and progressive disease (PD) in 22 patients (18%). Higher remission rates were positively correlated with high uptake on pretherapy somatostatin receptor imaging and a limited number of liver metastases, whereas PD was significantly more frequent in patients with a low performance score and extensive disease. Median time to progression in 103 patients who either had SD or tumor regression was more than 36 months.

CONCLUSION: Treatment with ¹⁷⁷Lu-octreotate results in tumor remission in a high percentage of patients with GEP tumors. Serious side effects are rare. The median time to progression compares favorably with chemotherapy. Results are better in patients with a limited tumor load. Therefore, early treatment, even in patients who have no PD, may be better.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. K. Kvols Revisiting C.G. Moertel's Land of Small Tumors J. Clin. Oncol., November 1, 2008; 26(31): 5005 - 5007. [Full Text] [PDF]

				S. Grozinsky-Glasberg, I. Shimon, M. Korbonits, and A. B Grossman Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms Endocr. Relat. Cancer, September 1, 2008; 15(3): 701 - 720. [Abstract] [Full Text] [PDF]

				M. Korner, B. Waser, and J. C. Reubi High Expression of Neuropeptide Y1 Receptors in Ewing Sarcoma Tumors Clin. Cancer Res., August 15, 2008; 14(16): 5043 - 5049. [Abstract] [Full Text] [PDF]

				S. Leboulleux, C. Dromain, A. L. Vataire, D. Malka, A. Auperin, J. Lumbroso, P. Duvillard, D. Elias, D. M. Hartl, T. De Baere, et al. Prediction and Diagnosis of Bone Metastases in Well-Differentiated Gastro-Entero-Pancreatic Endocrine Cancer: A Prospective Comparison of Whole Body Magnetic Resonance Imaging and Somatostatin Receptor Scintigraphy J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3021 - 3028. [Abstract] [Full Text] [PDF]

				D. J. Kwekkeboom, W. W. de Herder, B. L. Kam, C. H. van Eijck, M. van Essen, P. P. Kooij, R. A. Feelders, M. O. van Aken, and E. P. Krenning Treatment With the Radiolabeled Somatostatin Analog [177Lu-DOTA0,Tyr3]Octreotate: Toxicity, Efficacy, and Survival J. Clin. Oncol., May 1, 2008; 26(13): 2124 - 2130. [Abstract] [Full Text] [PDF]

				M. Ginj, H. Zhang, K.-P. Eisenwiener, D. Wild, S. Schulz, H. Rink, R. Cescato, J. C. Reubi, and H. R. Maecke New Pansomatostatin Ligands and Their Chelated Versions: Affinity Profile, Agonist Activity, Internalization, and Tumor Targeting Clin. Cancer Res., April 1, 2008; 14(7): 2019 - 2027. [Abstract] [Full Text] [PDF]

				G. Khanna, D. Bushnell, and M. S. O'Dorisio Utility of Radiolabeled Somatostatin Receptor Analogues for Staging/Restaging and Treatment of Somatostatin Receptor-Positive Pediatric Tumors Oncologist, April 1, 2008; 13(4): 382 - 389. [Abstract] [Full Text] [PDF]

				F. Iten, B. Muller, C. Schindler, C. Rochlitz, D. Oertli, H. R. Macke, J. Muller-Brand, and M. A. Walter 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., November 15, 2007; 13(22): 6696 - 6702. [Abstract] [Full Text] [PDF]

				W. J. G. Oyen, L. Bodei, F. Giammarile, H. R. Maecke, J. Tennvall, M. Luster, and B. Brans Targeted therapy in nuclear medicine current status and future prospects Ann. Onc., November 1, 2007; 18(11): 1782 - 1792. [Abstract] [Full Text] [PDF]

				M. H Kulke Gastrointestinal neuroendocrine tumors: a role for targeted therapies? Endocr. Relat. Cancer, June 1, 2007; 14(2): 207 - 219. [Abstract] [Full Text] [PDF]

				E. Vilar, R. Salazar, J. Perez-Garcia, J. Cortes, K. Oberg, and J. Tabernero Chemotherapy and role of the proliferation marker Ki-67 in digestive neuroendocrine tumors Endocr. Relat. Cancer, June 1, 2007; 14(2): 221 - 232. [Abstract] [Full Text] [PDF]

				M. Korner, M. Stockli, B. Waser, and J. C. Reubi GLP-1 Receptor Expression in Human Tumors and Human Normal Tissues: Potential for In Vivo Targeting J. Nucl. Med., May 1, 2007; 48(5): 736 - 743. [Abstract] [Full Text] [PDF]

				S. J. Mather, A. J. McKenzie, J. K. Sosabowski, T. M. Morris, D. Ellison, and S. A. Watson Selection of Radiolabeled Gastrin Analogs for Peptide Receptor-Targeted Radionuclide Therapy J. Nucl. Med., April 1, 2007; 48(4): 615 - 622. [Abstract] [Full Text] [PDF]

				M. Konijnenberg, M. Melis, R. Valkema, E. Krenning, and M. de Jong Radiation Dose Distribution in Human Kidneys by Octreotides in Peptide Receptor Radionuclide Therapy J. Nucl. Med., January 1, 2007; 48(1): 134 - 142. [Abstract] [Full Text] [PDF]

				D. O'Toole, A. Saveanu, A. Couvelard, G. Gunz, A. Enjalbert, P. Jaquet, P. Ruszniewski, and A. Barlier The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumours opens new therapeutic strategies Eur. J. Endocrinol., December 1, 2006; 155(6): 849 - 857. [Abstract] [Full Text] [PDF]

				D. Wild, M. Behe, A. Wicki, D. Storch, B. Waser, M. Gotthardt, B. Keil, G. Christofori, J. C. Reubi, and H. R. Macke [Lys40(Ahx-DTPA-111In)NH2]Exendin-4, a Very Promising Ligand for Glucagon-like Peptide-1 (GLP-1) Receptor Targeting J. Nucl. Med., December 1, 2006; 47(12): 2025 - 2033. [Abstract] [Full Text] [PDF]

				M. van Essen, E. P. Krenning, P. P. Kooij, W. H. Bakker, R. A. Feelders, W. W. de Herder, J. G. Wolbers, and D. J. Kwekkeboom Effects of Therapy with [177Lu-DOTA0, Tyr3]Octreotate in Patients with Paraganglioma, Meningioma, Small Cell Lung Carcinoma, and Melanoma J. Nucl. Med., October 1, 2006; 47(10): 1599 - 1606. [Abstract] [Full Text] [PDF]

				E. J. Rolleman, M. de Jong, R. Valkema, D. Kwekkeboom, B. Kam, and E. P. Krenning Inhibition of Kidney Uptake of Radiolabeled Somatostatin Analogs: Amino Acids or Gelofusine? J. Nucl. Med., October 1, 2006; 47(10): 1730 - 1731. [Full Text] [PDF]

				J. E.M. van Eerd, E. Vegt, J. F.M. Wetzels, F. G.M. Russel, R. Masereeuw, F. H.M. Corstens, O. C. Boerman, and W. J.G. Oyen Reply: Inhibition of Kidney Uptake of Radiolabeled Somatostatin Analogs: Amino Acids or Gelofusine? J. Nucl. Med., October 1, 2006; 47(10): 1731 - 1731. [Full Text] [PDF]

				M. Cremonesi, M. Ferrari, L. Bodei, G. Tosi, and G. Paganelli Dosimetry in Peptide Radionuclide Receptor Therapy: A Review J. Nucl. Med., September 1, 2006; 47(9): 1467 - 1475. [Abstract] [Full Text] [PDF]

				W. A. Weber Positron Emission Tomography As an Imaging Biomarker J. Clin. Oncol., July 10, 2006; 24(20): 3282 - 3292. [Abstract] [Full Text] [PDF]

				H. Uusijarvi, P. Bernhardt, F. Rosch, H. R. Maecke, and E. Forssell-Aronsson Electron- and Positron-Emitting Radiolanthanides for Therapy: Aspects of Dosimetry and Production J. Nucl. Med., May 1, 2006; 47(5): 807 - 814. [Abstract] [Full Text] [PDF]

				S. J. DeNardo Combined Molecular Targeting for Cancer Therapy: A New Paradigm in Need of Molecular Imaging J. Nucl. Med., January 1, 2006; 47(1): 4 - 5. [Full Text] [PDF]

				G. Vitale, W. W. de Herder, P. M. van Koetsveld, M. Waaijers, W. Schoordijk, E. Croze, A. Colao, S. W.J. Lamberts, and L. J. Hofland IFN-{beta} Is a Highly Potent Inhibitor of Gastroenteropancreatic Neuroendocrine Tumor Cell Growth In vitro Cancer Res., January 1, 2006; 66(1): 554 - 562. [Abstract] [Full Text] [PDF]