Neuroendocrine tumor

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This page is now exclusively focused on those tumors commonly called carcinoids, which may or may not be associated with the carcinoid syndrome; there are now separate pages for pancreatic NET and other endocrine cancers. Neuroendocrine tumors of unknown primary and poorly differentiated (high-grade) neuroendocrine tumors are usually treated with a small cell lung cancer regimen.

14 regimens on this page
20 variants on this page


Guidelines

ESMO

NCCN

All lines of therapy

Everolimus monotherapy

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Regimen

Study Evidence Comparator Efficacy Toxicity
Yao et al. 2015 (RADIANT-4) Phase III Placebo Superior PFS Equivalent HRQoL

Chemotherapy

Given until progression of disease, unacceptable toxicity, drug interruption of 3 weeks or longer, or withdrawal of consent

References

  1. Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Fave GD, Van Cutsem E, Tesselaar M, Shimada Y, Oh DY, Strosberg J, Kulke MH, Pavel ME; RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet. 2016 Mar 5;387(10022):968-977. Epub 2015 Dec 17. link to original article contains protocol PubMed
    1. HRQoL analysis: Pavel ME, Singh S, Strosberg JR, Bubuteishvili-Pacaud L, Degtyarev E, Neary MP, Carnaghi C, Tomasek J, Wolin E, Raderer M, Lahner H, Valle JW, Pommier R, Van Cutsem E, Tesselaar MET, Fave GD, Buzzoni R, Hunger M, Eriksson J, Cella D, Ricci JF, Fazio N, Kulke MH, Yao JC. Health-related quality of life for everolimus versus placebo in patients with advanced, non-functional, well-differentiated gastrointestinal or lung neuroendocrine tumours (RADIANT-4): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Oct;18(10):1411-1422. Epub 2017 Aug 30. link to original article PubMed

Interferon alfa-2b monotherapy

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Regimen

Study Evidence Comparator Efficacy
Faiss et al. 2003 Phase III Lanreotide Seems not superior
Lanreotide & Interferon alfa-2b Seems not superior

Immunotherapy

Given until progression of disease

Patients who progressed on monotherapy then received combination lanreotide & interferon alfa.

References

  1. Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed

Lanreotide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Faiss et al. 2003 Phase III Interferon alfa-2b Seems not superior
Lanreotide & Interferon alfa-2b Seems not superior

Endocrine therapy

Given until progression of disease

Patients who progressed on monotherapy then received combination lanreotide & interferon alfa.

References

  1. Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed

Lanreotide & Interferon alfa-2b

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Regimen

Study Evidence Comparator Efficacy
Faiss et al. 2003 Phase III Interferon alfa-2b Seems not superior
Lanreotide Seems not superior

Endocrine & Immunotherapy

References

  1. Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed

Octreotide monotherapy

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Regimen #1

Study Evidence
Oberg et al. 2004 Consensus guideline

Endocrine therapy

  • Octreotide (Sandostatin) 0.1 to 0.5 mg SC given 2 to 4 times per day, with dose increased by doubling the dose every 3 to 4 days as needed to control symptoms
    • "A reasonable starting dose is" 0.15 mg SC TID

Treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms

Regimen #2

Study Evidence
Kvols et al. 1986 Phase II

Endocrine therapy

"Treatment was continued for as long as a clinical improvement was maintained"

Regimen #3

Study Evidence Comparator Efficacy
Kölby et al. 2003 Randomized Phase II Octreotide & Interferon alfa Inferior TTP

Endocrine therapy

  • Octreotide (Sandostatin) 0.1 mg SC BID; patients with persistent carcinoid symptoms could receive increased doses up to 0.2 mg SC TID

References

  1. Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986 Sep 11;315(11):663-6. link to original article contains verified protocol PubMed
  2. Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32(2):225-9. link to original article PubMed
  3. Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. link to original article contains verified protocol PubMed
  4. Review: Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. link to original article contains verified protocol PubMed

Octreotide LAR monotherapy

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Regimen #1

Study Evidence Comparator Efficacy
Rinke et al. 2009 (PROMID) Phase III Placebo Superior TTP
Pavel et al. 2011 (RADIANT-2) Phase III Octreotide LAR & Everolimus Seems to have inferior PFS

Endocrine therapy

28-day cycles, given until progression of disease

Regimen #2

Study Evidence
Oberg et al. 2004 Consensus guideline

Endocrine therapy

  • Octreotide LAR (Sandostatin LAR) 20 to 30 mg IM once on day 1, with potentially higher doses if needed for symptom control
    • "As a general rule, if the total [octreotide] IR dose is 200 to 600 mcg/day [0.2 to 0.6 mg/day], LAR 20 mg should be tried, and if total IR dose is 750 to 1500 mcg/day [0.75 to 1.5 mg/day], LAR 30 mg should be tried."
  • Octreotide (Sandostatin) (dose not specified) SC as needed for additional symptom control

28-day cycles; treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms

References

  1. Review: Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. link to original article contains verified protocol PubMed
  2. Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; 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 Oct 1;27(28):4656-63. Epub 2009 Aug 24. link to original article contains verified protocol PubMed
  3. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. 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 Dec 10;378(9808):2005-12. Epub 2011 Nov 25. link to original article contains verified protocol PubMed

Octreotide & Everolimus

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Regimen #1

Study Evidence Comparator Efficacy
Pavel et al. 2011 (RADIANT-2) Phase III Octreotide LAR Seems to have superior PFS

Endocrine & Chemotherapy

Given until progression of disease or unacceptable toxicity

Regimen #2

Study Evidence
Yao et al. 2008 Phase II

Note: Everolimus "dose of 10 mg was associated with superior PFS...however, the study was not prospectively powered for these comparisons. These analyses should be considered exploratory."

Endocrine & Chemotherapy

28-day cycle for up to 12 cycles or until progression of disease, though treatment could be continued beyond this period if thought by the treating physician to be beneficial

References

  1. Yao JC, Phan AT, Chang DZ, Wolff RA, Hess K, Gupta S, Jacobs C, Mares JE, Landgraf AN, Rashid A, Meric-Bernstam F. Efficacy of RAD001 (everolimus) and octreotide LAR in advanced low- to intermediate-grade neuroendocrine tumors: results of a phase II study. J Clin Oncol. 2008 Sep 10;26(26):4311-8. link to original article contains verified protocol link to PMC article PubMed
  2. Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. 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 Dec 10;378(9808):2005-12. Epub 2011 Nov 25. link to original article contains verified protocol PubMed

Octreotide & Interferon alfa

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Regimen

Study Evidence Comparator Efficacy
Kölby et al. 2003 Randomized Phase II Octreotide LAR Superior TTP

Kölby et al. 2003 did not specifically say whether Interferon alfa-2b (Intron-A) or Interferon alfa-2a (Roferon-A) was used.

Endocrine & Immunotherapy

References

  1. Janson ET, Oberg K. Long-term management of the carcinoid syndrome. Treatment with octreotide alone and in combination with alpha-interferon. Acta Oncol. 1993;32(2):225-9. link to original article PubMed
  2. Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. link to original article contains verified protocol PubMed

Placebo

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Regimen

Study Evidence Comparator Efficacy
Rinke et al. 2009 (PROMID) Phase III Octreotide LAR Inferior TTP

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

  1. Rinke A, Müller HH, Schade-Brittinger C, Klose KJ, Barth P, Wied M, Mayer C, Aminossadati B, Pape UF, Bläker M, Harder J, Arnold C, Gress T, Arnold R; 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 Oct 1;27(28):4656-63. Epub 2009 Aug 24. link to original article contains verified protocol PubMed

Temozolomide monotherapy

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Regimen

Study Evidence
Ekeblad et al. 2007 Phase II

Chemotherapy

  • Temozolomide (Temodar) as follows:
    • Cycle 1: 100 or 150 mg/m2 PO once per day on days 1 to 5
    • Cycle 2 onwards: increased as tolerated up to 200 mg/m2 PO once per day on days 1 to 5

Supportive medications

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Ekeblad S, Sundin A, Janson ET, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Orlefors H, Sigurd M, Oberg K, Eriksson B, Skogseid B. Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clin Cancer Res. 2007 May 15;13(10):2986-91. link to original article contains verified protocol PubMed
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