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Shortened interval of long-acting octreotide administration is effective in patients with well-differentiated neuroendocrine carcinomas in progression on standard doses

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Abstract

Background: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited antiproliferative effects. Aim: The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations (21 days) in WD-NET patients with progressive disease at standard-dose interval. Subjects and methods: Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled. Clinical, biological, and objective tumor response was evaluated after LAR 30 mg every 21 days. Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days. Results: The treatment with LAR 30 mg every 21 days resulted in complete and partial control of clinical symptoms in 40% and 60% of cases, respectively. Circulating neuroendocrine markers were significantly decreased in 30% of cases. A stabilization of disease was obtained in 93% and objective response in 7%. The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the standard one (30 vs 9 months, p<0.0001). The treatment was safe and well tolerated. Conclusions: The shortened schedule of LAR administration was able to re-institute control of clinical symptoms, to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a standard schedule treatment.

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References

  1. Plöckinger U, Rindi G, Arnold R, et al; European Neuroendocrine Tumour Society. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS). Neuroendocrinology 2004, 80: 394–424.

    Article  PubMed  CAS  Google Scholar 

  2. Kaltsas GA, Besser GM, Grossman AB. The diagnosis and medical management of advanced neuroendocrine tumors. Endocr Rev 2004, 25: 458–511.

    Article  PubMed  CAS  Google Scholar 

  3. Oberg K, Kvols L, Caplin M, et al. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 2004, 15: 966–73.

    Article  PubMed  CAS  Google Scholar 

  4. Saltz L, Trochanowski B, Buckley M, et al. Octreotide as an antineoplastic agent in the treatment of functional and non-functional neuroendocrine tumors. Cancer 1993, 72: 244–8.

    Article  PubMed  CAS  Google Scholar 

  5. Arnold R, Benning R, Neuhaus C, Rolwage M, Trautmann ME. Gastroenteropancreatic endocrine tumours: effect of Sandostatin on tumour growth. The German Sandostatin Study Group. Digestion 1993, 54(Suppl 1): 72–5.

    Article  PubMed  Google Scholar 

  6. Scherübl H, Wiedenmann B, Riecken EO, Thomas F, Böhme E, Räth U. Treatment of the carcinoid syndrome with a depot formulation of the somatostatin analogue lanreotide. Eur J Cancer 1994, 30A: 1590–1.

    Article  PubMed  Google Scholar 

  7. Tomassetti P, Migliori M, Gullo L Slow-release lanreotide treatment in endocrine gastrointestinal tumors. Am J Gastroenterol 1998, 93: 1468–71.

    Article  PubMed  CAS  Google Scholar 

  8. Eriksson B, Oberg K. Summing up 15 years of somatostatin analog therapy in neuroendocrine tumors: future outlook. Ann Oncol 1999, 10: 31–8.

    Article  Google Scholar 

  9. Anthony L, Johnson D, Hande K, et al. Somatostatin analogue phase I trials in neuroendocrine neoplasms. Acta Oncol 1993, 32: 217–23.

    Article  PubMed  CAS  Google Scholar 

  10. di Bartolomeo M, Bajetta E, Buzzoni R, et al. Clinical efficacy of octreotide in the treatment of metastatic neuroendocrine tumors. A study by the Italian Trials in Medical Oncology Group. Cancer 1996, 77: 402–8.

    Article  PubMed  Google Scholar 

  11. Eriksson B, Renstrup J, Imam H, Oberg K. High-dose treatment with lanreotide of patients with advanced neuroendocrine gastrointestinal tumors: clinical and biological effects. Ann Oncol 1997, 8: 1041–4.

    Article  PubMed  CAS  Google Scholar 

  12. Faiss S, Räth U, Mansmann U, et al. Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion 1999, 60: 469–76.

    Article  PubMed  CAS  Google Scholar 

  13. Rubin J, Ajani J, Schirmer W, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol 1999, 17: 600–6.

    PubMed  CAS  Google Scholar 

  14. Wymenga AN, Eriksson B, Salmela PI, et al. Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. J Clin Oncol 1999, 17: 1111.

    PubMed  CAS  Google Scholar 

  15. Bajetta E, Procopio G, Catena L, et al. Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study. Cancer 2006, 107: 2474–81.

    Article  PubMed  CAS  Google Scholar 

  16. Welin SV, Janson ET, Sundin A, et al. High-dose treatment with a long-acting somatostatin analogue in patients with advanced midgut carcinoid tumours. Eur J Endocrinol 2004, 151: 107–112.

    Article  PubMed  CAS  Google Scholar 

  17. Solcia E, Klöppel G, Sobin LH. Histological typing of endocrine tumours, WHO international histological classification of tumours. Berlin: Springer Verlag, 2000.

    Book  Google Scholar 

  18. Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. Pathology & Genetics: Tumours of the Lung, Pleura, Thymus and Heart, WHO International Histological Classification of Tumours. Lyon: IARC Press, 2004.

    Google Scholar 

  19. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009, 45: 228–47.

    Article  PubMed  CAS  Google Scholar 

  20. Rinke A, Müller HH, Schade-Brittinger C, et al; PROMID Study Group. 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: 4656–63.

    Article  PubMed  CAS  Google Scholar 

  21. Oberg K, Jelic S; ESMO Guidelines Working Group. Neuroendocrine bronchial and thymic tumors: ESMO clinical recommendation for diagnosis, treatment and follow-up. Ann Oncol 2008, 19(Suppl 2): ii102–3.

    PubMed  Google Scholar 

  22. Oberg K, Jelic S; ESMO Guidelines Working Group. Neuroendocrine gastroenteropancreatic tumors: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2008, 19(Suppl 2): 104–5.

    Google Scholar 

  23. Hofland LJ, Lamberts SW. The pathophysiological consequences of somatostatin receptor internalization and resistance. Endocr Rev 2003, 24: 28–47.

    Article  PubMed  CAS  Google Scholar 

  24. Astruc B, Marbach P, Bouterfa H, et al. Long-acting octreotide and prolonged-release lanreotide formulations have different pharmacokinetic profiles. J Clin Pharmacol 2005, 45: 836–44.

    Article  PubMed  CAS  Google Scholar 

  25. Chen T, Miller TF, Prasad P, et al. Pharmacokinetics, pharmacodynamics, and safety of microencapsulated octreotide acetate in healthy subjects. J Clin Pharmacol 2000, 40: 475–81.

    Article  PubMed  Google Scholar 

  26. Colao A, Pivonello R, Auriemma RS, Galdiero M, Savastano S, Lombardi G. Beneficial effect of dose escalation of octreotide-LAR as first-line therapy in patients with acromegaly. Eur J Endocrinol 2007, 157: 579–87.

    Article  PubMed  CAS  Google Scholar 

  27. Giustina A, Bonadonna S, Bugari G, et al. High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial. Eur J Endocrinol 2009, 161: 331–8.

    Article  PubMed  CAS  Google Scholar 

  28. Imam H, Eriksson B, Lukinius A, et al. Induction of apoptosis in neuroendocrine tumors of the digestive system during treatment with somatostatin analogs. Acta Oncol 1997, 36: 607–14.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to A. Faggiano MD, PhD.

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P.F. and A.F. equally contributed to the paper.

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Ferolla, P., Faggiano, A., Grimaldi, F. et al. Shortened interval of long-acting octreotide administration is effective in patients with well-differentiated neuroendocrine carcinomas in progression on standard doses. J Endocrinol Invest 35, 326–331 (2012). https://doi.org/10.3275/7869

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