Revision as of 12:58, 17 October 2022

Back to Top

Section editor transclusions Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: for more general neuroendocrine regimens, please visit the neuroendocrine tumors page.

0 regimens on this page 0 variants on this page

Guidelines

ESMO

2020: Pavel et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Older

2012: Öberg et al. Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

NANETS

2020: Halfdanarson et al. The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors
2020: Howe et al. The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors

NCCN

NCCN Guidelines - Neuroendocrine Tumors

All lines of therapy

Capecitabine & Temozolomide

Regimen

Study	Evidence
Strosberg et al. 2011	Retrospective

Chemotherapy

Capecitabine (Xeloda) 750 mg/m² PO twice per day on days 1 to 14
Temozolomide (Temodar) 200 mg/m² PO once per day at bedtime on days 10 to 14

Supportive therapy

Ondansetron (Zofran) 8 mg (route not specified) once per day on days 1 to 14, prior to Temozolomide (Temodar)

28-day cycles

References

Retrospective: Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, Helm J, Kvols L. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011 Jan 15;117(2):268-75. Epub 2010 Sep 7. link to original article contains dosing details in manuscript link to PMC article PubMed

Doxorubicin & Streptozocin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Moertel et al. 1992	1978-1985	Phase 3 (E-switch-ic)	1. Chlorozotocin	Superior OS
Moertel et al. 1992	1978-1985	Phase 3 (E-switch-ic)	2. 5-FU & Streptozocin	Superior OS

Chemotherapy

Doxorubicin (Adriamycin) 50 mg/m² IV once per day on days 1 & 22
Streptozocin (Zanosar) 500 mg/m² IV once per day on days 1 to 5

42-day cycles

References

Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23. link to original article contains dosing details in manuscript PubMed

Everolimus monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Yao et al. 2010 (RADIANT-1)	2006-2007	Phase 2
Yao et al. 2011 (RADIANT-3)	2007-2009	Phase 3 (E-RT-esc)	Placebo	Superior PFS Median PFS: 11 vs 4.6 mo (HR 0.35, 95% CI 0.27-0.45)

Targeted therapy

Everolimus (Afinitor) 10 mg PO once per day

Continued indefinitely

References

RADIANT-1: Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O'Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010 Jan 1;28(1):69-76. Epub 2009 Nov 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00363051
RADIANT-3: Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00510068
1. Update: Yao JC, Pavel M, Lombard-Bohas C, Van Cutsem E, Voi M, Brandt U, He W, Chen D, Capdevila J, de Vries EGE, Tomassetti P, Hobday T, Pommier R, Öberg K. Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: overall survival and circulating biomarkers from the randomized, phase III RADIANT-3 study. J Clin Oncol. 2016 Nov 10;34(32):3906-3913. Epub 2016 Sep 30. link to original article link to PMC article PubMed
Review: Yao JC, Phan AT, Jehl V, Shah G, Meric-Bernstam F. Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience. Cancer Res. 2013 Mar 1;73(5):1449-53. Epub 2013 Feb 22. link to original article PubMed
COMPETE: NCT03049189
COMPOSE: NCT04919226

Everolimus & Octreotide

Regimen variant #1

Study	Years of enrollment	Evidence
Yao et al. 2008	2005-2006	Phase 2

Targeted therapy

Everolimus (Afinitor) 5 mg PO once per day

Endocrine therapy

Octreotide LAR (Sandostatin LAR) 30 mg IM once on day 1

28-day cycles

Regimen variant #2

Study	Years of enrollment	Evidence
Yao et al. 2008	2005-2006	Phase 2
Yao et al. 2010 (RADIANT-1)	2006-2007	Phase 2

Note: In Yao et al. 2008, 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." Patients in RADIANT-1 who received this regimen had already been receiving octreotide LAR for at least 3 months before participating in the study; they were continued on their prestudy dose up to 30 mg.

Targeted therapy

Everolimus (Afinitor) 10 mg PO once per day

Endocrine therapy

Octreotide LAR (Sandostatin LAR) 30 mg IM once on day 1

28-day cycles

References

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 dosing details in manuscript link to PMC article PubMed
RADIANT-1: Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O'Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010 Jan 1;28(1):69-76. Epub 2009 Nov 23. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00363051

FAS

FAS: Fluorouracil, Adriamycin (Doxorubicin), Streptozocin

Regimen

Study	Evidence
Kouvaraki et al. 2004	Retrospective

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 to 5
Doxorubicin (Adriamycin) 40 mg/m² IV bolus once on day 1
Streptozocin (Zanosar) 400 mg/m² IV bolus once per day on days 1 to 5

28-day cycles

References

Retrospective: Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004 Dec 1;22(23):4762-71. link to original article contains dosing details in manuscript PubMed

Fluorouracil & Streptozocin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Moertel et al. 1980	1972-1978	Phase 3 (E-esc)	Fluorouracil	Might have superior OS
Moertel et al. 1992	1978-1985	Phase 3 (C)	1. Chlorozotocin	Did not meet endpoint of OS
Moertel et al. 1992	1978-1985	Phase 3 (C)	2. Doxorubicin & Streptozocin	Inferior OS

Note: treatment details are from Moertel et al. 1992.

Chemotherapy

Streptozocin (Zanosar) 500 mg/m² IV once per day on days 1 to 5
Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 to 5

42-day cycles

References

Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980 Nov 20;303(21):1189-94. link to original article PubMed
Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23. link to original article contains dosing details in manuscript PubMed

Lanreotide Depot/Autogel monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Caplin et al. 2014 (CLARINET)	2006-2013	Phase 3 (E-RT-esc)	Placebo	Superior PFS Median PFS: NYR vs 18 mo (HR 0.47, 95% CI 0.30-0.73)
Caplin et al. 2016 (CLARINET OLE)	2009-NR	Non-randomized

Endocrine therapy

Lanreotide (Somatuline) Depot/Autogel 120 mg SC once on day 1

28-day cycle for 96 weeks (CLARINET) or up to 8 years (CLARINET OLE)

References

CLARINET: Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. link to original article contains dosing details in manuscript PubMed NCT00353496
CLARINET OLE: Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Gomez-Panzani E, Ruszniewski P; CLARINET Investigators. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016 Mar;23(3):191-9. Epub 2016 Jan 7. link to original article link to PMC article PubMed NCT00842348

Lanreotide & Interferon alfa-2b

Regimen

Study	Evidence
Fjällskog et al. 2002	Pilot, <20 pts

Note: Fjällskog et al. 2002 contained case reports of several patients treated with lanreotide & interferon alfa. Each patient received individualized therapy rather than a standard regimen.

Endocrine therapy

Lanreotide (Somatuline) 3 mg SC twice per day

Immunotherapy

Interferon alfa-2b (Intron-A) 3,000,000 to 5,000,000 units SC once per day, 3 to 7 days per week (total of 9,000,000 to 25,000,000 units per week)

References

Fjällskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19(1):35-42. link to original article PubMed

Octreotide monotherapy

Regimen

Study	Evidence
Oberg et al. 2004	Consensus guideline

Endocrine therapy

Octreotide (Sandostatin) 0.1 to 0.5 mg SC given two to four 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 three times per day

Continued indefinitely

References

Review: Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. 2001 Jun;81(3):527-42. link to original article PubMed
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 dosing details in manuscript PubMed

Octreotide LAR monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Rinke et al. 2009 (PROMID)	2001-2008	Phase 3 (E-esc)	Placebo	Superior TTP Median TTP: 14.3 vs 6 mo (HR 0.34, 95% CI 0.20-0.59)

Endocrine therapy

Octreotide LAR (Sandostatin LAR) 30 mg IM once on day 1, with potentially higher doses if needed for symptom control

28-day cycles

References

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 dosing details in manuscript PubMed
PROMID: 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 dosing details in manuscript PubMed NCT00171873
NETTER-1: Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01578239
1. Update: Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. link to original article PubMed
NETTER-2: NCT03972488

Octreotide & Interferon alfa

Regimen

Study	Evidence
Fjällskog et al. 2002	Pilot, <20 pts

Note: Fjällskog et al. 2002 contained case reports of several patients treated with octreotide & interferon alfa. Each patient received individualized therapy rather than a standard regimen.

Endocrine therapy

Octreotide (Sandostatin) 0.05 to 0.5 mg SC given two to three times per day

Immunotherapy

Interferon alfa-2b (Intron-A) 3,000,000 to 5,000,000 units SC once per day, 3 to 7 days per week (total of 9,000,000 to 25,000,000 units per week)

References

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
Fjällskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19(1):35-42. link to original article PubMed

Lutetium Lu 177 dotatate & Octreotide LAR

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Strosberg et al. 2017 (NETTER-1)	2012-2016	Phase 3 (E-switch-ooc)	Octreotide LAR; high-dose	Superior PFS Median PFS: NYR vs 8.4 mo (HR 0.21, 95% CI 0.13-0.33)	More cytopenias (neutropenia, thrombocytopenia and lymphopenia)

Note: patients had well-differentiated (Ki67 less than 20%) midgut neuroendocrine tumors with somatostatin receptors present in all target lesions

Endocrine therapy

Octreotide LAR (Sandostatin LAR) 30 mg SC once on day 1, given 2 hours after each lutetium Lu 177 dotatate infusion

4-week cycles

Radioconjugate therapy

Lutetium Lu 177 dotatate (Lutathera) 7.4 GBq (200 mCi) IV once on day 1

Supportive therapy

For renal protection, an IV amino acid solution was administered concomitantly for at least 4 hours, starting 30 minutes prior to drug infusion.

8-week cycle for 4 cycles

References

NETTER-1: Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01578239
1. Update: Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. link to original article PubMed

Sunitinib monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Raymond et al. 2011 (A6181111)	2007-2009	Phase 3 (E-RT-esc)	Placebo	Superior PFS¹ Median PFS: 12.6 vs 5.8 mo (HR 0.32, 95% CI 0.18-0.55)	More diarrhea; seems to have worse insomnia

¹Reported efficacy is based on the 2017 update.
Note: while the initial publication seemed to have a significant survival advantage for this arm (p=0.02), this finding was no longer significant at the final update (p=0.094). The primary endpoint (PFS) remains significant.

Targeted therapy

Sunitinib (Sutent) 37.5 mg PO once per day

Continued indefinitely

References

A6181111: Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13. Erratum in: N Engl J Med. 2011 Mar 17;364(11):1082. link to original article contains dosing details in manuscript PubMed NCT00428597
1. HRQoL analysis: Vinik A, Bottomley A, Korytowsky B, Bang YJ, Raoul JL, Valle JW, Metrakos P, Hörsch D, Mundayat R, Reisman A, Wang Z, Chao RC, Raymond E. Patient-reported outcomes and quality of life with sunitinib versus placebo for pancreatic neuroendocrine tumors: results from an international phase III trial. Target Oncol. 2016 Dec;11(6):815-824. link to original article PubMed
2. Update: Faivre S, Niccoli P, Castellano D, Valle JW, Hammel P, Raoul JL, Vinik A, Van Cutsem E, Bang YJ, Lee SH, Borbath I, Lombard-Bohas C, Metrakos P, Smith D, Chen JS, Ruszniewski P, Seitz JF, Patyna S, Lu DR, Ishak KJ, Raymond E. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study. Ann Oncol. 2017 Feb 1;28(2):339-343. link to original article PubMed

Temozolomide monotherapy

Regimen

Study	Evidence
Ekeblad et al. 2007	Retrospective

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 therapy

Tropisetron (Navoban) (dose/route/schedule not specified) routinely used as an antiemetic

28-day cycles

References

Retrospective: 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 dosing details in manuscript PubMed

Temozolomide & Bevacizumab

Regimen

Study	Years of enrollment	Evidence
Chan et al. 2012 (DFCI 04-272)	2004-2005	Phase 2

Chemotherapy

Temozolomide (Temodar) 150 mg/m² PO once per day on days 1 to 7, 15 to 21

Targeted therapy

Bevacizumab (Avastin) 5 mg/kg IV once per day on days 1 & 15

Supportive therapy

PCP prophylaxis: Trimethoprim-Sulfamethoxazole (Bactrim DS) 160/800 mg PO once every Monday, Wednesday, and Friday
- Allergic patients received alternate prophylaxis
VZV prophylaxis: Acyclovir (Zovirax) 400 mg PO three times per day

28-day cycles

References

DFCI 04-272: Chan JA, Stuart K, Earle CC, Clark JW, Bhargava P, Miksad R, Blaszkowsky L, Enzinger PC, Meyerhardt JA, Zheng H, Fuchs CS, Kulke MH. Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. J Clin Oncol. 2012 Aug 20;30(24):2963-8. Epub 2012 Jul 9. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00137774

Temozolomide & Thalidomide

Regimen

Study	Evidence
Kulke et al. 2006	Phase 2

Chemotherapy

Temozolomide (Temodar) 150 mg/m² PO once per day on days 1 to 7, 15 to 21

Targeted therapy

Thalidomide (Thalomid) 200 mg PO once per day

28-day cycles

References

Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Vincitore M, Michelini A, Fuchs CS. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006 Jan 20;24(3):401-6. link to original article contains dosing details in manuscript PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|heme}}
+{{#lst:Section editor transclusions|giei}}
+''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Pancreatic NET - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br>
+<big>Note: for more general neuroendocrine regimens, please visit the '''[[neuroendocrine tumors]]''' page.</big>
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 11: / Line 13: @@
 {{TOC limit|limit=3}}
 =Guidelines=
-==ASH==
+==[http://www.esmo.org/ ESMO]==
-*'''2019:''' Neunert et al. [https://ashpublications.org/bloodadvances/article/3/23/3829/429213/American-Society-of-Hematology-2019-guidelines-for American Society of Hematology 2019 guidelines for immune thrombocytopenia]
+*'''2020:''' Pavel et al. [https://doi.org/10.1016/j.annonc.2020.03.304 Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 ===Older===
-*'''2011:''' Neunert et al. [http://www.bloodjournal.org/content/117/16/4190 The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia]
+*'''2012:''' Öberg et al. [https://www.esmo.org/Guidelines/Endocrine-and-Neuroendocrine-Cancers/Neuroendocrine-Gastroenteropancreatic-Tumours Neuroendocrine gastro-entero-pancreatic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
-==BSH==
+==NANETS==
-*'''2019:''' Hill et al. [https://doi.org/10.1111/bjh.15735 The prevention of glucocorticoid-induced osteoporosis in patients with immune thrombocytopenia receiving steroids: a British Society for Haematology Good Practice Paper]
+*'''2020:''' Halfdanarson et al. [https://doi.org/10.1097/mpa.0000000000001597 The North American Neuroendocrine Tumor Society Consensus Guidelines for Surveillance and Medical Management of Pancreatic Neuroendocrine Tumors]
-=="How I Treat"==
+*'''2020:''' Howe et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7029300/ The North American Neuroendocrine Tumor Society Consensus Paper on the Surgical Management of Pancreatic Neuroendocrine Tumors]
-*'''2021:''' Ghanima et al. [https://doi.org/10.1182/blood.2021010968 How I treat primary ITP in adult patients who are unresponsive to or dependent on corticosteroid treatment]
+==[https://www.nccn.org/ NCCN]==
-=Initial therapy=
+*[https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf NCCN Guidelines - Neuroendocrine Tumors]
-==Dexamethasone monotherapy {{#subobject:7c8c62|Regimen=1}}==
+=All lines of therapy=
+==Capecitabine & Temozolomide {{#subobject:738284|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:666055|Variant=1}}===
+===Regimen {{#subobject:fc2dd9|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 25%" |Study
+! style="width: 50%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/127/3/296.long Wei et al. 2015]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665634/ Strosberg et al. 2011]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#ffffbe" |Retrospective
-|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#1a9850" |Superior CR rate
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Chemotherapy====
-*[[Dexamethasone (Decadron)]] 40 mg/day PO on days 1 to 4
+*[[Capecitabine (Xeloda)]] 750 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-'''4-day course'''
+*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day at bedtime on days 10 to 14
-</div>
+====Supportive therapy====
-<div class="toccolours" style="background-color:#cbd5e7">
+*[[Ondansetron (Zofran)]] 8 mg (route not specified) once per day on days 1 to 14, prior to [[Temozolomide (Temodar)]]
-====Subsequent treatment====
+'''28-day cycles'''
-*If platelets remained below 30 x 10<sup>9</sup>/L or bleeding by day 10, course is repeated once
+</div></div>
-</div></div><br>
+===References===
+# '''Retrospective:''' Strosberg JR, Fine RL, Choi J, Nasir A, Coppola D, Chen DT, Helm J, Kvols L. First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer. 2011 Jan 15;117(2):268-75. Epub 2010 Sep 7. [https://doi.org/10.1002/cncr.25425 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665634/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20824724 PubMed]
+==Doxorubicin & Streptozocin {{#subobject:5c625d|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:678fa4|Variant=1}}===
+===Regimen {{#subobject:a9c7ed|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 20%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1056/NEJM199202203260804 Moertel et al. 1992]
+|rowspan=2|1978-1985
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|1. [[#Chlorozotocin_monotherapy_88|Chlorozotocin]]
+| style="background-color:#1a9850" |Superior OS
 |-
-|[http://www.bloodjournal.org/content/122/21/325 Matschke et al. 2013]
+|2. [[#Fluorouracil_.26_Streptozocin|5-FU & Streptozocin]]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9850" |Superior OS
-|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#91cf60" |Seems to have superior responding patients maintaining remission for at least 6 mo
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy, part 1====
+====Chemotherapy====
-*[[Prednisone (Sterapred)]] 1 mg/kg/day PO for 7 days
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 22
-====Immunosuppressive therapy, part 2====
+*[[Streptozocin (Zanosar)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Dexamethasone (Decadron)]] 0.6 mg/kg/day (route not specified) for days 1 to 4
+'''42-day cycles'''
-'''21-day cycle for 6 cycles'''
+</div></div>
-</div></div><br>
+===References===
+# Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23. [https://doi.org/10.1056/NEJM199202203260804 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1310159 PubMed]
+==Everolimus monotherapy {{#subobject:78dff1|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3 {{#subobject:19f4e9|Variant=1}}===
+===Regimen {{#subobject:5ea369|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 20%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa030254 Cheng et al. 2003]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ Yao et al. 2010 (RADIANT-1)]
+|2006-2007
 | style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ Yao et al. 2011 (RADIANT-3)]
+|2007-2009
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Pancreatic_NET_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 11 vs 4.6 mo<br>(HR 0.35, 95% CI 0.27-0.45)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Targeted therapy====
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+*[[Everolimus (Afinitor)]] 10 mg PO once per day
-'''4-day course'''
+'''Continued indefinitely'''
-''Patients who had an initial response, but whose platelets dropped below 30 x 10<sup>9</sup>/L within 6 months received:''
+</div></div>
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+===References===
-*[[Prednisone (Sterapred)]] 15 mg PO once per day, starting on day 5, "with gradual tapering"
+# '''RADIANT-1:''' Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O'Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010 Jan 1;28(1):69-76. Epub 2009 Nov 23. [https://doi.org/10.1200/jco.2009.24.2669 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19933912 PubMed] NCT00363051
-</div></div><br>
+# '''RADIANT-3:''' Yao JC, Shah MH, Ito T, Bohas CL, Wolin EM, Van Cutsem E, Hobday TJ, Okusaka T, Capdevila J, de Vries EG, Tomassetti P, Pavel ME, Hoosen S, Haas T, Lincy J, Lebwohl D, Öberg K; RAD001 in Advanced Neuroendocrine Tumors Third Trial (RADIANT-3) Study Group. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):514-23. [https://doi.org/10.1056/NEJMoa1009290 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21306238 PubMed] NCT00510068
+## '''Update:''' Yao JC, Pavel M, Lombard-Bohas C, Van Cutsem E, Voi M, Brandt U, He W, Chen D, Capdevila J, de Vries EGE, Tomassetti P, Hobday T, Pommier R, Öberg K. Everolimus for the treatment of advanced pancreatic neuroendocrine tumors: overall survival and circulating biomarkers from the randomized, phase III RADIANT-3 study. J Clin Oncol. 2016 Nov 10;34(32):3906-3913. Epub 2016 Sep 30. [https://doi.org/10.1200/JCO.2016.68.0702 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5791842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27621394 PubMed]
+# '''Review:''' Yao JC, Phan AT, Jehl V, Shah G, Meric-Bernstam F. Everolimus in advanced pancreatic neuroendocrine tumors: the clinical experience. Cancer Res. 2013 Mar 1;73(5):1449-53. Epub 2013 Feb 22. [http://cancerres.aacrjournals.org/content/73/5/1449.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/23436795 PubMed]
+#'''COMPETE:''' NCT03049189
+#'''COMPOSE:''' NCT04919226
+==Everolimus & Octreotide {{#subobject:d6b3eb|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, monthly dexamethasone {{#subobject:f892de|Variant=1}}===
+===Regimen variant #1 {{#subobject:b0f62f|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/109/4/1401.long Mazzucconi et al. 2007]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ Yao et al. 2008]
+|2005-2006
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Targeted therapy====
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+*[[Everolimus (Afinitor)]] 5 mg PO once per day
-*Patients who had platelet counts of less than or equal to 20 x 10<sup>9</sup>/L between cycles received [[Prednisone (Sterapred)]] 0.25 mg/kg PO once per day "between courses"
+====Endocrine therapy====
-'''28-day cycle for 6 cycles'''
+*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1
+'''28-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, bi-weekly dexamethasone {{#subobject:8ac5fe|Variant=1}}===
+===Regimen variant #2 {{#subobject:f82bb5|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/109/4/1401.long Mazzucconi et al. 2007]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ Yao et al. 2008]
+|2005-2006
 | style="background-color:#91cf61" |Phase 2
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ Yao et al. 2010 (RADIANT-1)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2006-2007
-====Immunosuppressive therapy====
+| style="background-color:#91cf61" |Phase 2
-*[[Dexamethasone (Decadron)]] by the following criteria:
-**Adults: 40 mg IV or PO once per day on days 1 to 4
-**Patients less than 15 years old: 20 mg/m<sup>2</sup> (maximum dose of 40 mg) IV or PO once per day on days 1 to 4
-**Patients who had platelet counts of less than or equal to 30 x 10<sup>9</sup>/L between cycles and/or who had bleeding related to thrombocytopenia received 0.035 mg/kg PO once per day "between courses"
-'''14-day cycle for 4 cycles'''
-</div></div>
-===References===
-# Cheng Y, Wong RS, Soo YO, Chui CH, Lau FY, Chan NP, Wong WS, Cheng G. Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone. N Engl J Med. 2003 Aug 28;349(9):831-6. [https://doi.org/10.1056/NEJMoa030254 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12944568 PubMed] content property of [http://hemonc.org HemOnc.org]
-# Mazzucconi MG, Fazi P, Bernasconi S, De Rossi G, Leone G, Gugliotta L, Vianelli N, Avvisati G, Rodeghiero F, Amendola A, Baronci C, Carbone C, Quattrin S, Fioritoni G, D'Alfonso G, Mandelli F; Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA) Thrombocytopenia Working Party. Therapy with high-dose dexamethasone (HD-DXM) in previously untreated patients affected by idiopathic thrombocytopenic purpura: a GIMEMA experience. Blood. 2007 Feb 15;109(4):1401-7. Epub 2006 Oct 31. [http://www.bloodjournal.org/content/109/4/1401.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17077333 PubMed]
-# '''Abstract:''' Johannes Matschke, Hannes Müller-Beißenhirtz, Ilona Vester, Bernd Hertenstein, Lewin Eisele, Hildegard Lax, Claudia Ose, Ulrich Dührsen. A Randomized Trial Of Daily Prednisone Versus Pulsed Dexamethasone In Treatment Naïve Patients With Idiopathic Thrombocytopenic Purpura. Blood Nov 2013,122(21)325. [http://www.bloodjournal.org/content/122/21/325 link to abstract]
-# Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. [http://www.bloodjournal.org/content/127/3/296.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26480931 PubMed]
-==Dexamethasone & Eltrombopag {{#subobject:910687|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:470504|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[http://www.bloodjournal.org/content/123/25/3906.long Gómez-Almaguer et al. 2014]
-| style="background-color:#ffffbe" |Pilot, <20 pts reported
 |-
 |}
+''Note: In Yao et al. 2008, 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." Patients in RADIANT-1 who received this regimen had already been receiving octreotide LAR for at least 3 months before participating in the study; they were continued on their prestudy dose up to 30 mg.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Targeted therapy====
-*[[Dexamethasone (Decadron)]] 40 mg/day PO on days 1 to 4
+*[[Everolimus (Afinitor)]] 10 mg PO once per day
-====Growth factor therapy====
+====Endocrine therapy====
-*[[Eltrombopag (Promacta)]] 50 mg PO once per day on days 5 to 33
+*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1
-'''5-week course'''
+'''28-day cycles'''
-</div></div>
-===References===
-<!-- Presented in an abstract form at the 55th meeting of the American Society of Hematology, New Orleans, LA, December 2013. -->
-# Gómez-Almaguer D, Herrera-Rojas MA, Jaime-Pérez JC, Gómez-De León A, Cantú-Rodríguez OG, Gutiérrez-Aguirre CH, Tarín-Arzaga L, Hernández-Reyes J, Ruiz-Arguelles GJ. Eltrombopag and high-dose dexamethasone as frontline treatment of newly diagnosed immune thrombocytopenia in adults. Blood. 2014 Jun 19;123(25):3906-8. Epub 2014 May 6. [http://www.bloodjournal.org/content/123/25/3906.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24802773 PubMed]
-==Dexamethasone & Mycophenolate mofetil {{#subobject:5f56yh|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:5yh112|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1056/nejmoa2100596 Bradbury et al. 2021 (FLIGHT)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#Dexamethasone_monotherapy|Dexamethasone]]<br> 2. [[#Prednisolone_monotherapy_88|Prednisolone]]
-| style="background-color:#1a9850" |Superior treatment failure
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
-*[[Dexamethasone (Decadron)]]
-*[[Mycophenolate mofetil (CellCept)]]
 </div></div>
 ===References===
-#'''FLIGHT:''' Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. [https://doi.org/10.1056/nejmoa2100596 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34469646/ PubMed] NCT03156452
+# 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. [https://doi.org/10.1200/jco.2008.16.7858 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18779618 PubMed]
-==Dexamethasone & Rituximab {{#subobject:b9a6ee|Regimen=1}}==
+# '''RADIANT-1:''' Yao JC, Lombard-Bohas C, Baudin E, Kvols LK, Rougier P, Ruszniewski P, Hoosen S, St Peter J, Haas T, Lebwohl D, Van Cutsem E, Kulke MH, Hobday TJ, O'Dorisio TM, Shah MH, Cadiot G, Luppi G, Posey JA, Wiedenmann B. Daily oral everolimus activity in patients with metastatic pancreatic neuroendocrine tumors after failure of cytotoxic chemotherapy: a phase II trial. J Clin Oncol. 2010 Jan 1;28(1):69-76. Epub 2009 Nov 23. [https://doi.org/10.1200/jco.2009.24.2669 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19933912 PubMed] NCT00363051
+==FAS {{#subobject:66b05e|Regimen=1}}==
+FAS: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>S</u>'''treptozocin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen ("R+3Dex") {{#subobject:d05adc|Variant=1}}===
+===Regimen {{#subobject:de76a2|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/122/21/2310 Imahiyerobo et al. 2013]
+|[https://doi.org/10.1200/jco.2004.04.024 Kouvaraki et al. 2004]
 | style="background-color:#ffffbe" |Retrospective
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Chemotherapy====
-*[[Dexamethasone (Decadron)]] 28 mg/m<sup>2</sup>/day (maximum dose of 40 mg) on days 1 to 4
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Rituximab (Rituxan)]] as follows:
+*[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV bolus once on day 1
-**Cycles 1 & 2: 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Streptozocin (Zanosar)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-'''14-day cycle for 3 cycles'''
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''Abstract: Retrospective:''' Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. [http://www.bloodjournal.org/content/122/21/2310 link to abstract]
+# '''Retrospective:''' Kouvaraki MA, Ajani JA, Hoff P, Wolff R, Evans DB, Lozano R, Yao JC. Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol. 2004 Dec 1;22(23):4762-71. [https://doi.org/10.1200/jco.2004.04.024 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15570077 PubMed]
-==Intravenous immunoglobulin monotherapy {{#subobject:ea894c|Regimen=1}}==
+==Fluorouracil & Streptozocin {{#subobject:6f7b84|Regimen=1}}==
-IVIG: '''<u>I</u>'''ntra'''<u>V</u>'''enous '''<u>I</u>'''mmuno'''<u>G</u>'''lobulin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9134b2|Variant=1}}===
+===Regimen {{#subobject:e45011|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 20%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1046/j.1365-2141.1999.01766.x Godeau et al. 1999]
+|[https://doi.org/10.1056/NEJM198011203032101 Moertel et al. 1980]
+|1972-1978
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Intravenous_immunoglobulin_monotherapy|IVIG]]; 0.5 g/kg
+|[[#Fluorouracil_monotherapy_88|Fluorouracil]]
-| style="background-color:#1a9850" |Superior response rate
+| style="background-color:#d9ef8b" |Might have superior OS
-|}
+|-
-<div class="toccolours" style="background-color:#b3e2cd">
+| rowspan="2" |[https://doi.org/10.1056/NEJM199202203260804 Moertel et al. 1992]
-====Supportive therapy====
+|rowspan=2|1978-1985
-*[[Intravenous immunoglobulin (IVIG)]] 1000 mg/kg IV once on day 1
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-'''One dose'''
+|1. [[#Chlorozotocin_monotherapy_88|Chlorozotocin]]
-</div></div>
+| style="background-color:#ffffbf" |Did not meet endpoint of OS
-===References===
-# Imbach P, Wagner HP, Berchtold W, Gaedicke G, Hirt A, Joller P, Mueller-Eckhardt C, Müller B, Rossi E, Barandun S. Intravenous immunoglobulin versus oral corticosteroids in acute immune thrombocytopenic purpura in childhood. Lancet. 1985 Aug 31;2(8453):464-8. [https://doi.org/10.1016/s0140-6736(85)90400-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2863492 PubMed]
-# Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr. 1993 Dec;123(6):989-95. [https://doi.org/10.1016/s0022-3476(05)80400-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8229536 PubMed]
-# Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M, Esseltine D, Chan KW, de Veber B, Israels S, Kobrinsky N, Luke B. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. 1994 Sep 10;344(8924):703-7. [https://doi.org/10.1016/s0140-6736(94)92205-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7915773 PubMed]
-# Godeau B, Caulier MT, Decuypere L, Rose C, Schaeffer A, Bierling P. Intravenous immunoglobulin for adults with autoimmune thrombocytopenic purpura: results of a randomized trial comparing 05 and 1 g/kg bw. Br J Haematol. 1999 Dec;107(4):716-9. [https://doi.org/10.1046/j.1365-2141.1999.01766.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10606875 PubMed]
-# Godeau B, Chevret S, Varet B, Lefrère F, Zini JM, Bassompierre F, Chèze S, Legouffe E, Hulin C, Grange MJ, Fain O, Bierling P; French ATIP Study Group. Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial. Lancet. 2002 Jan 5;359(9300):23-9. [https://doi.org/10.1016/S0140-6736(02)07275-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11809183 PubMed]
-# '''TIKI:''' Heitink-Pollé KMJ, Uiterwaal CSPM, Porcelijn L, Tamminga RYJ, Smiers FJ, van Woerden NL, Wesseling J, Vidarsson G, Laarhoven AG, de Haas M, Bruin MCA; TIKI Investigators. Intravenous immunoglobulin vs observation in childhood immune thrombocytopenia: a randomized controlled trial. Blood. 2018 Aug 30;132(9):883-891. Epub 2018 Jun 26. [http://www.bloodjournal.org/content/132/9/883.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/29945954 PubMed]
-==Mycophenolate mofetil & Prednisolone {{#subobject:5f5dab|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:dacj12|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://doi.org/10.1056/nejmoa2100596 Bradbury et al. 2021 (FLIGHT)]
+|2. [[#Doxorubicin_.26_Streptozocin|Doxorubicin & Streptozocin]]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#d73027" |Inferior OS
-|1. [[#Dexamethasone_monotherapy|Dexamethasone]]<br> 2. [[#Prenisolone_monotherapy_88|Prednisolone]]
-| style="background-color:#1a9850" |Superior treatment failure
 |-
 |}
+''Note: treatment details are from Moertel et al. 1992.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Chemotherapy====
-*[[Mycophenolate mofetil (CellCept)]]
+*[[Streptozocin (Zanosar)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Prednisolone (Millipred)]]
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+'''42-day cycles'''
 </div></div>
 ===References===
-#'''FLIGHT:''' Bradbury CA, Pell J, Hill Q, Bagot C, Cooper N, Ingram J, Breheny K, Kandiyali R, Rayment R, Evans G, Talks K, Thomas I, Greenwood R. Mycophenolate Mofetil for First-Line Treatment of Immune Thrombocytopenia. N Engl J Med. 2021 Sep 2;385(10):885-895. [https://doi.org/10.1056/nejmoa2100596 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34469646/ PubMed] NCT03156452
+# Moertel CG, Hanley JA, Johnson LA. Streptozocin alone compared with streptozocin plus fluorouracil in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1980 Nov 20;303(21):1189-94. [https://doi.org/10.1056/NEJM198011203032101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6252466 PubMed]
-==Prednisone monotherapy {{#subobject:5f27f2|Regimen=1}}==
+# Moertel CG, Lefkopoulo M, Lipsitz S, Hahn RG, Klaassen D. Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med. 1992 Feb 20;326(8):519-23. [https://doi.org/10.1056/NEJM199202203260804 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1310159 PubMed]
+==Lanreotide Depot/Autogel monotherapy {{#subobject:8bca3a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:d3c7eb|Variant=1}}===
+===Regimen {{#subobject:a9ee08|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 20%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.bloodjournal.org/content/127/3/296.long Wei et al. 2015]
+|[https://doi.org/10.1056/NEJMoa1316158 Caplin et al. 2014 (CLARINET)]
-| style="background-color:#1a9851" |Phase 3 (C)
+|2006-2013
-|[[#Dexamethasone_monotherapy|Dexamethasone]]
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-| style="background-color:#d73027" |Inferior CR rate
+|[[Pancreatic_NET_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 18 mo<br>(HR 0.47, 95% CI 0.30-0.73)
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740728/ Caplin et al. 2016 (CLARINET OLE)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2009-NR
-====Immunosuppressive therapy====
+| style="background-color:#91cf61" |Non-randomized
-*[[Prednisone (Sterapred)]] as follows:
+| style="background-color:#d3d3d3" |
-**Days 1 to 28: 1 mg/kg/day PO
+| style="background-color:#d3d3d3" |
-**Day 29 onwards: tapered over 4 to 6 weeks with a goal of maintenance dosing less than 15 mg/day or "complete termination"
-***Taper schedule determined by treating physician
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:7c003e|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[http://www.bloodjournal.org/content/122/21/325 Matschke et al. 2013]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Dexamethasone_monotherapy|Dexamethasone]]
-| style="background-color:#fc8d59" |Seems to have inferior responding patients maintaining remission for at least 6 mo
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Endocrine therapy====
-*[[Prednisone (Sterapred)]] as follows:
+*[[Lanreotide (Somatuline) | Lanreotide (Somatuline) Depot/Autogel]] 120 mg SC once on day 1
-**Weeks 1 to 2: 1 mg/kg/day PO
+'''28-day cycle for 96 weeks (CLARINET) or up to 8 years (CLARINET OLE)'''
-**Weeks 3 to 19: Tapered over 19 weeks with a goal of maintenance dosing less than 7.5 mg/day at the end of week 19
 </div></div>
 ===References===
-# Blanchette VS, Luke B, Andrew M, Sommerville-Nielsen S, Barnard D, de Veber B, Gent M. A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura. J Pediatr. 1993 Dec;123(6):989-95. [https://doi.org/10.1016/s0022-3476(05)80400-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8229536 PubMed]
+# '''CLARINET:''' Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P; CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014 Jul 17;371(3):224-33. [https://doi.org/10.1056/NEJMoa1316158 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25014687 PubMed] NCT00353496
-# Blanchette V, Imbach P, Andrew M, Adams M, McMillan J, Wang E, Milner R, Ali K, Barnard D, Bernstein M, Esseltine D, Chan KW, de Veber B, Israels S, Kobrinsky N, Luke B. Randomised trial of intravenous immunoglobulin G, intravenous anti-D, and oral prednisone in childhood acute immune thrombocytopenic purpura. Lancet. 1994 Sep 10;344(8924):703-7. [https://doi.org/10.1016/s0140-6736(94)92205-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7915773 PubMed]
+# '''CLARINET OLE:''' Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Gomez-Panzani E, Ruszniewski P; CLARINET Investigators. Anti-tumour effects of lanreotide for pancreatic and intestinal neuroendocrine tumours: the CLARINET open-label extension study. Endocr Relat Cancer. 2016 Mar;23(3):191-9. Epub 2016 Jan 7. [https://doi.org/10.1530/erc-15-0490 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740728/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26743120 PubMed] NCT00842348
-# '''Abstract:''' Johannes Matschke, Hannes Müller-Beißenhirtz, Ilona Vester, Bernd Hertenstein, Lewin Eisele, Hildegard Lax, Claudia Ose, Ulrich Dührsen. A Randomized Trial Of Daily Prednisone Versus Pulsed Dexamethasone In Treatment Naïve Patients With Idiopathic Thrombocytopenic Purpura. Blood Nov 2013,122(21)325. [http://www.bloodjournal.org/content/122/21/325 link to abstract]
+==Lanreotide & Interferon alfa-2b {{#subobject:9c5a59|Regimen=1}}==
-# Wei Y, Ji XB, Wang YW, Wang JX, Yang EQ, Wang ZC, Sang YQ, Bi ZM, Ren CA, Zhou F, Liu GQ, Peng J, Hou M. High-dose dexamethasone vs prednisone for treatment of adult immune thrombocytopenia: a prospective multicenter randomized trial. Blood. 2016 Jan 21;127(3):296-302. Epub 2015 Oct 19. [http://www.bloodjournal.org/content/127/3/296.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26480931 PubMed]
-==RhIG monotherapy {{#subobject:3ab9b6|Regimen=1}}==
-RhIG: '''<u>Rh</u>'''o(D) '''<u>I</u>'''mmune '''<u>G</u>'''lobulin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 25 mcg/kg {{#subobject:8335a6|Variant=1}}===
+===Regimen {{#subobject:652f4d|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/77/9/1884 Bussel et al. 1991]
+|[http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 Fjällskog et al. 2002]
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#ffffbe" |Pilot, <20 pts
 |-
 |}
-''Eligibility: RhD-positive.''
+''Note: Fjällskog et al. 2002 contained case reports of several patients treated with lanreotide & interferon alfa. Each patient received individualized therapy rather than a standard regimen.''
-====Supportive therapy====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Rho(D) immune globulin (RhoGAM)]] 25 mcg/kg IV once on day 1, repeated as needed on days 3 & 4
+====Endocrine therapy====
-'''4-day course'''
+*[[Lanreotide (Somatuline)]] 3 mg SC twice per day
-</div></div><br>
+====Immunotherapy====
-<div class="toccolours" style="background-color:#eeeeee">
+*[[Interferon alfa-2b (Intron-A)]] 3,000,000 to 5,000,000 units SC once per day, 3 to 7 days per week (total of 9,000,000 to 25,000,000 units per week)
-===Regimen variant #2, 50 mcg/kg {{#subobject:487067|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1046/j.1365-2141.2001.02627.x Newman et al. 2001]
-| style="background-color:#91cf61" |Randomized Phase 2, <20 pts (C)
-|[[#RhIG_monotherapy|Rho(D)]]; 75 mcg/kg
-| style="background-color:#fc8d59" |Seems to have inferior platelet effect
-|-
-|}
-''Eligibility: RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 10<sup>9</sup>/L.''
-====Supportive therapy====
-*[[Rho(D) immune globulin (RhoGAM)]] 50 mcg/kg IV once on day 1
-====Supportive therapy====
-*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 1, prior to therapy
-*[[Prednisone (Sterapred)]] 20 mg PO once on day 1, prior to therapy
-'''One dose; can be repeated if required to increase platelet count'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 75 mcg/kg {{#subobject:b30788|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1046/j.1365-2141.2001.02627.x Newman et al. 2001]
-| style="background-color:#91cf61" |Randomized Phase 2, <20 pts (E-esc)
-|[[#RhIG_monotherapy|Rho(D)]]; 50 mcg/kg
-| style="background-color:#91cf60" |Seems to have superior platelet effect
-|-
-|}
-''Eligibility: RhD-positive, adult, HIV-negative, non-splenectomized, platelet count less than or equal to 30 x 10<sup>9</sup>/L.''
-====Supportive therapy====
-*[[Rho(D) immune globulin (RhoGAM)]] 75 mcg/kg IV once on day 1
-====Supportive therapy====
-*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 1, prior to therapy
-*[[Prednisone (Sterapred)]] 20 mg PO once on day 1, prior to therapy
-'''One dose; can be repeated if required to increase platelet count'''
 </div></div>
 ===References===
-# Bussel JB, Graziano JN, Kimberly RP, Pahwa S, Aledort LM. Intravenous anti-D treatment of immune thrombocytopenic purpura: analysis of efficacy, toxicity, and mechanism of effect. Blood. 1991 May 1;77(9):1884-93. [http://www.bloodjournal.org/content/77/9/1884 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1850307 PubMed]
+# Fjällskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19(1):35-42. [http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12025889 PubMed]
-# Newman GC, Novoa MV, Fodero EM, Lesser ML, Woloski BM, Bussel JB. A dose of 75 microg/kg/day of iv anti-D increases the platelet count more rapidly and for a longer period of time than 50 microg/kg/day in adults with immune thrombocytopenic purpura. Br J Haematol. 2001 Mar;112(4):1076-8. [https://doi.org/10.1046/j.1365-2141.2001.02627.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11298610 PubMed]
+==Octreotide monotherapy {{#subobject:665a8b|Regimen=1}}==
-==TT4 {{#subobject:d5ad89|Regimen=1}}==
-TT4: '''<u>T</u>'''riple '''<u>T</u>'''herapy (4?)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:be2a8d|Variant=1}}===
+===Regimen {{#subobject:cd8cf6|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560338/ Choi et al. 2015]
+|[https://doi.org/10.1093/annonc/mdh216 Oberg et al. 2004]
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#ffffbe" |Consensus guideline
-|-
-|}
-''The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.''
-====Immunosuppressive therapy====
-*[[Dexamethasone (Decadron)]] 40 mg/day PO on days 1 to 4
-*[[Cyclosporine|Cyclosporine A]] 2.5 to 3 mg/kg/day PO on days 1 to 28
-**Dose adjusted for target trough of 200 to 400 mcg/L
-*[[Rituximab (Rituxan)]] 100 mg IV once per day on days 7, 14, 21, 28
-</div></div>
-===References===
-# Choi PY, Roncolato F, Badoux X, Ramanathan S, Ho SJ, Chong BH. A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4). Blood. 2015 Jul 23;126(4):500-3. Epub 2015 May 13. [http://www.bloodjournal.org/content/126/4/500.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4560338/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25972158 PubMed]
-=Relapsed or refractory=
-==ATRA & Danazol {{#subobject:43e110|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:077574|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S2352-3026(17)30170-9 Feng et al. 2017 (U1111-1132-6877)]
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[[#Danazol_monotherapy|Danazol]]
-| style="background-color:#1a9850" |Superior 12-month sustained response
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[All-trans retinoic acid (ATRA)]] 10 mg PO twice per day
 ====Endocrine therapy====
-*[[Danazol (Danocrine)]] 200 mg PO twice per day
+*[[Octreotide (Sandostatin)]] 0.1 to 0.5 mg SC given two to four times per day, with dose increased by doubling the dose every 3 to 4 days as needed to control symptoms
-'''16-week course'''
+**"A reasonable starting dose is" 0.15 mg SC three times per day
+'''Continued indefinitely'''
 </div></div>
 ===References===
-# '''U1111-1132-6877:''' Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. [https://doi.org/10.1016/S2352-3026(17)30170-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28917657 PubMed] NCT01667263
+# '''Review:''' Brentjens R, Saltz L. Islet cell tumors of the pancreas: the medical oncologist's perspective. Surg Clin North Am. 2001 Jun;81(3):527-42. [https://doi.org/10.1016/s0039-6109(05)70141-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11459269 PubMed]
-==Avatrombopag monotherapy {{#subobject:c8da29|Regimen=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. [https://doi.org/10.1093/annonc/mdh216 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15151956 PubMed]
+==Octreotide LAR monotherapy {{#subobject:e356ea|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:1aab54|Variant=1}}===
+===Regimen {{#subobject:f0bc1b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 20%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1111/bjh.15573 Jurczak et al. 2018 (E5501-G000-302)]
+|[https://doi.org/10.1200/jco.2009.22.8510 Rinke et al. 2009 (PROMID)]
+|2001-2008
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
+|[[Pancreatic_NET_-_null_regimens#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior cumulative weeks of platelet response
+| style="background-color:#1a9850" |Superior TTP<br>Median TTP: 14.3 vs 6 mo<br>(HR 0.34, 95% CI 0.20-0.59)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Growth factor therapy====
+====Endocrine therapy====
-*[[Avatrombopag (Doptelet)]]
+*[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1, with potentially higher doses if needed for symptom control
+'''28-day cycles'''
 </div></div>
 ===References===
-# Bussel JB, Kuter DJ, Aledort LM, Kessler CM, Cuker A, Pendergrass KB, Tang S, McIntosh J. A randomized trial of avatrombopag, an investigational thrombopoietin-receptor agonist, in persistent and chronic immune thrombocytopenia. Blood. 2014 Jun 19;123(25):3887-94. Epub 2014 May 6. [http://www.bloodjournal.org/content/123/25/3887.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/24802775 PubMed]
+# '''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. [https://doi.org/10.1093/annonc/mdh216 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15151956 PubMed]
-# '''E5501-G000-302:''' Jurczak W, Chojnowski K, Mayer J, Krawczyk K, Jamieson BD, Tian W, Allen LF. Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia. Br J Haematol. 2018 Nov;183(3):479-490. Epub 2018 Sep 7. [https://doi.org/10.1111/bjh.15573 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30191972 PubMed]
+# '''PROMID:''' 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. [https://doi.org/10.1200/jco.2009.22.8510 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19704057 PubMed] NCT00171873
-==Cyclosporine monotherapy {{#subobject:4d3847|Regimen=1}}==
+# '''NETTER-1:''' Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. [https://doi.org/10.1056/NEJMoa1607427 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28076709 PubMed] NCT01578239
+## '''Update:''' Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. [https://doi.org/10.1016/s1470-2045(21)00572-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34793718/ PubMed]
+#'''NETTER-2:''' NCT03972488
+==Octreotide & Interferon alfa {{#subobject:1cf4c5|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:df1b55|Variant=1}}===
+===Regimen {{#subobject:cbf5c4|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/99/4/1482 Emilia et al. 2002]
+|[http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 Fjällskog et al. 2002]
 | style="background-color:#ffffbe" |Pilot, <20 pts
 |-
 |}
-''The authors do not specify whether modified or non-modified cyclosporine was used in this protocol. Please contact them for clarifications.''
+''Note: Fjällskog et al. 2002 contained case reports of several patients treated with octreotide & interferon alfa. Each patient received individualized therapy rather than a standard regimen.''
-====Immunosuppressive therapy====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cyclosporine|Cyclosporine A]] as follows:
+====Endocrine therapy====
-**Days 1 to 6: 5 mg/kg/day PO split into twice per day dosing
+*[[Octreotide (Sandostatin)]] 0.05 to 0.5 mg SC given two to three times per day
-**Day 7 onwards: 2.5 to 3 mg/kg/day PO with dose adjusted for target trough of 200 to 400 mcg/L
+====Immunotherapy====
+*[[Interferon alfa-2b (Intron-A)]] 3,000,000 to 5,000,000 units SC once per day, 3 to 7 days per week (total of 9,000,000 to 25,000,000 units per week)
 </div></div>
 ===References===
-# Emilia G, Morselli M, Luppi M, Longo G, Marasca R, Gandini G, Ferrara L, D'Apollo N, Potenza L, Bertesi M, Torelli G. Long-term salvage therapy with cyclosporin A in refractory idiopathic thrombocytopenic purpura. Blood. 2002 Feb 15;99(4):1482-5. [http://www.bloodjournal.org/content/99/4/1482 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11830504 PubMed]
+# 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. [https://doi.org/10.3109/02841869309083916 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7686765 PubMed]
-==Danazol monotherapy {{#subobject:e7bf80|Regimen=1}}==
+# Fjällskog ML, Sundin A, Westlin JE, Oberg K, Janson ET, Eriksson B. Treatment of malignant endocrine pancreatic tumors with a combination of alpha-interferon and somatostatin analogs. Med Oncol. 2002;19(1):35-42. [http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12025889 PubMed]
+==Lutetium Lu 177 dotatate & Octreotide LAR {{#subobject:ee13c4|Regimen=1}} ==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:9a63e6|Variant=1}}===
+===Regimen {{#subobject:33d0ef|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 17%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 15%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+!style="width: 17%"|Comparator
-|-
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|[https://doi.org/10.1056/NEJM198306093082306 Ahn et al. 1983]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-| style="background-color:#91cf61" |Pilot, >20 pts
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
-|[https://doi.org/10.1016/S2352-3026(17)30170-9 Feng et al. 2017 (U1111-1132-6877)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ Strosberg et al. 2017 (NETTER-1)]
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
+|2012-2016
-|[[#ATRA_.26_Danazol|ATRA & Danazol]]
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-| style="background-color:#d73027" |Inferior 12-month sustained response
+| [[#Octreotide_LAR_monotherapy|Octreotide LAR]]; high-dose
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 8.4 mo<br>(HR 0.21, 95% CI 0.13-0.33)
+| style="background-color:#d73027" |More cytopenias (neutropenia, thrombocytopenia and lymphopenia)
 |-
 |}
-''Note: Ahn et al. 1983 gave a range of 200 mg PO from two to four times per day; the dose below is from U1111-1132-6877''
+''Note: patients had well-differentiated (Ki67 less than 20%) midgut neuroendocrine tumors with somatostatin receptors present in all target lesions''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Danazol (Danocrine)]] 200 mg PO twice per day
+* [[Octreotide LAR (Sandostatin LAR)]] 30 mg SC once on day 1, '''given 2 hours after each lutetium Lu 177 dotatate infusion'''
-'''16-week course'''
+'''4-week cycles'''
+====Radioconjugate therapy====
+* [[Lutetium Lu 177 dotatate (Lutathera)]] 7.4 GBq (200 mCi) IV once on day 1
+====Supportive therapy====
+* For renal protection, an IV amino acid solution was administered concomitantly for at least 4 hours, starting 30 minutes prior to drug infusion.
+'''8-week cycle for 4 cycles'''
 </div></div>
 ===References===
-# Ahn YS, Harrington WJ, Simon SR, Mylvaganam R, Pall LM, So AG. Danazol for the treatment of idiopathic thrombocytopenic purpura. N Engl J Med. 1983 Jun 9;308(23):1396-9. [https://doi.org/10.1056/NEJM198306093082306 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/6682484 PubMed]
+# '''NETTER-1:''' Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, Krenning E; NETTER-1 Trial Investigators. Phase 3 trial of (177)Lu-dotatate for midgut neuroendocrine tumors. N Engl J Med. 2017 Jan 12;376(2):125-135. [https://doi.org/10.1056/NEJMoa1607427 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5895095/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28076709 PubMed] NCT01578239
-# '''U1111-1132-6877:''' Feng FE, Feng R, Wang M, Zhang JM, Jiang H, Jiang Q, Lu J, Liu H, Peng J, Hou M, Shen JL, Wang JW, Xu LP, Liu KY, Huang XJ, Zhang XH. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial. Lancet Haematol. 2017 Oct;4(10):e487-e496. Epub 2017 Sep 13. [https://doi.org/10.1016/S2352-3026(17)30170-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28917657 PubMed] NCT01667263
+## '''Update:''' Strosberg JR, Caplin ME, Kunz PL, Ruszniewski PB, Bodei L, Hendifar A, Mittra E, Wolin EM, Yao JC, Pavel ME, Grande E, Van Cutsem E, Seregni E, Duarte H, Gericke G, Bartalotta A, Mariani MF, Demange A, Mutevelic S, Krenning EP; NETTER-1 investigators. 177Lu-Dotatate plus long-acting octreotide versus high‑dose long-acting octreotide in patients with midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2021 Dec;22(12):1752-1763. Epub 2021 Nov 15. [https://doi.org/10.1016/s1470-2045(21)00572-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34793718/ PubMed]
-==Dexamethasone monotherapy {{#subobject:a6cd06|Regimen=1}}==
+==Sunitinib monotherapy {{#subobject:ee13d2|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8c260f|Variant=1}}===
+===Regimen {{#subobject:80d0ef|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 17%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 15%"|Years of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://doi.org/10.1056/NEJM199406023302203 Andersen 1994]
+|[https://doi.org/10.1056/NEJMoa1003825 Raymond et al. 2011 (A6181111)]
-| style="background-color:#ffffbe" |Pilot, <20 pts
+|2007-2009
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Pancreatic_NET_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS<sup>1</sup><br>Median PFS: 12.6 vs 5.8 mo<br>(HR 0.32, 95% CI 0.18-0.55)
+| style="background-color:#d73027" |More diarrhea; seems to have worse insomnia
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2017 update.''<br>
+''Note: while the initial publication seemed to have a significant survival advantage for this arm (p=0.02), this finding was no longer significant at the final update (p=0.094). The primary endpoint (PFS) remains significant.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Targeted therapy====
-*[[Dexamethasone (Decadron)]] 40 mg PO once per day on days 1 to 4
+*[[Sunitinib (Sutent)]] 37.5 mg PO once per day
-'''28-day cycles for 6 cycles'''
+'''Continued indefinitely'''
 </div></div>
 ===References===
-# Andersen JC. Response of resistant idiopathic thrombocytopenic purpura to pulsed high-dose dexamethasone therapy. N Engl J Med. 1994 Jun 2;330(22):1560-4. [https://doi.org/10.1056/NEJM199406023302203 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8177245 PubMed]
+# '''A6181111:''' Raymond E, Dahan L, Raoul JL, Bang YJ, Borbath I, Lombard-Bohas C, Valle J, Metrakos P, Smith D, Vinik A, Chen JS, Hörsch D, Hammel P, Wiedenmann B, Van Cutsem E, Patyna S, Lu DR, Blanckmeister C, Chao R, Ruszniewski P. Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med. 2011 Feb 10;364(6):501-13. Erratum in: N Engl J Med. 2011 Mar 17;364(11):1082. [https://doi.org/10.1056/NEJMoa1003825 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21306237 PubMed] NCT00428597
-==Dexamethasone & Rituximab {{#subobject:52f32|Regimen=1}}==
+## '''HRQoL analysis:''' Vinik A, Bottomley A, Korytowsky B, Bang YJ, Raoul JL, Valle JW, Metrakos P, Hörsch D, Mundayat R, Reisman A, Wang Z, Chao RC, Raymond E. Patient-reported outcomes and quality of life with sunitinib versus placebo for pancreatic neuroendocrine tumors: results from an international phase III trial. Target Oncol. 2016 Dec;11(6):815-824. [https://doi.org/10.1007/s11523-016-0462-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27924459 PubMed]
+## '''Update:''' Faivre S, Niccoli P, Castellano D, Valle JW, Hammel P, Raoul JL, Vinik A, Van Cutsem E, Bang YJ, Lee SH, Borbath I, Lombard-Bohas C, Metrakos P, Smith D, Chen JS, Ruszniewski P, Seitz JF, Patyna S, Lu DR, Ishak KJ, Raymond E. Sunitinib in pancreatic neuroendocrine tumors: updated progression-free survival and final overall survival from a phase III randomized study. Ann Oncol. 2017 Feb 1;28(2):339-343. [https://doi.org/10.1093/annonc/mdw561 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27836885 PubMed]
+==Temozolomide monotherapy {{#subobject:69ae1c|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen ("R+3Dex") {{#subobject:abae3b|Variant=1}}===
+===Regimen {{#subobject:6aac4c|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/122/21/2310 Imahiyerobo et al. 2013]
+|[http://clincancerres.aacrjournals.org/content/13/10/2986.long Ekeblad et al. 2007]
 | style="background-color:#ffffbe" |Retrospective
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Chemotherapy====
-*[[Dexamethasone (Decadron)]] 28 mg/m<sup>2</sup>/day (maximum dose of 40 mg) on days 1 to 4
+*[[Temozolomide (Temodar)]] as follows:
-*[[Rituximab (Rituxan)]] as follows:
+**Cycle 1: 100 or 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
-**Cycles 1 & 2: 375 mg/m<sup>2</sup> IV once per day on days 1 & 8
+**Cycle 2 onwards: increased as tolerated up to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
-'''14-day cycle for 3 cycles'''
+====Supportive therapy====
+*[[Tropisetron (Navoban)]] (dose/route/schedule not specified) routinely used as an antiemetic
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''Abstract:''' Allison Imahiyerobo, Micha Thompson, Marina Izak Karaev, Waleed Ghanima, James B Bussel. Rituximab Combined With Three Cycles Of High Dose Dexamethasone Provides a Long Term Response Rate Similar To That Of Splenectomy In Patients With Immune Thrombocytopenia (ITP) Of Duration Less Than 2 Years. Blood Nov 2013,122(21)2310. [http://www.bloodjournal.org/content/122/21/2310 link to abstract]
+# '''Retrospective:''' 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. [http://clincancerres.aacrjournals.org/content/13/10/2986.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17505000 PubMed]
-==Eltrombopag monotherapy {{#subobject:170bd|Regimen=1}}==
+==Temozolomide & Bevacizumab {{#subobject:ce7fe6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:90336c|Variant=1}}===
+===Regimen {{#subobject:be3718|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 25%" |Study
+!style="width: 33%"|Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
-! style="width: 25%" |Comparator
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(15)61107-2 Grainger et al. 2015 (PETIT2)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior durable platelet response
-|-
-|}
-''This regimen was intended for pediatric patients.''
-====Growth factor therapy====
-*[[Eltrombopag (Promacta)]] with starting dose by the following criteria:
-**Age 6 to 17, weighing at least 27kg, non-east Asian: 50 mg PO once per day
-**Age 6 to 17, weighing at least 27kg, east Asian: 25 mg PO once per day
-**Age 6 to 17, weighing less than 27kg, non-east Asian: 37.5 mg PO once per day
-**Age 6 to 17, weighing less than 27kg, east Asian: 25 mg PO once per day
-**Age 1 to 5, non-east Asian: 1.2 mg/kg/day oral suspension
-**Age 1 to 5, east Asian: 0.8 mg/kg/day oral suspension
-'''Dose adjusted to a maximum of 75 mg/day, with temporary discontinuation for platelet count greater than 400 x 10<sup>9</sup>/L'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:5912e7|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(09)60402-5 Bussel et al. 2009 (TRA100773)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior plt count of greater than or equal to 50 x 10<sup>9</sup>/L on day 43
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Growth factor therapy====
-*[[Eltrombopag (Promacta)]] 50 mg (starting dose) PO once per day
-'''The dose could be increased from 50 mg to 75 mg after 3 weeks in patients whose platelet counts were less than 50 x 10<sup>9</sup>/L. Treatment was discontinued in patients who attained a platelet count greater than 200 x 10<sup>9</sup>/L'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3 {{#subobject:9ac7d2|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(10)60959-2 Cheng et al. 2010 (RAISE-ITP)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior RR
-|-
-|}
-''Note: this trial should not be confused with the trial by the same name in colorectal cancer.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Growth factor therapy====
-*[[Eltrombopag (Promacta)]] 50 mg PO once per day, with dose modifications:
-**Increase to 75 mg PO once per day allowed after day 22 for patients with platelet counts lower than 50 x 10<sup>9</sup>/L
-**Decrease to 25 mg PO once per day required for platelets counts between 200 and 400 x 10<sup>9</sup>/L
-**Drug was held for platelet count greater than 400 x 10<sup>9</sup>/L, until platelet count dropped below 150 x 10<sup>9</sup>/L
-'''6-month course'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4 {{#subobject:b1f517|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1056/NEJMoa073275 Bussel et al. 2007 (TRA100773)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior RR
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Growth factor therapy====
-*[[Eltrombopag (Promacta)]] 50 mg PO once per day
-'''Up to 6-week course'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5 {{#subobject:55f69d|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.bloodjournal.org/content/121/3/537.long Saleh et al. 2012 (EXTEND)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874232/ Chan et al. 2012 (DFCI 04-272)]
+|2004-2005
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Growth factor therapy====
+====Chemotherapy====
-*[[Eltrombopag (Promacta)]] 50 mg PO once per day, with adjustments:
+*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 7, 15 to 21
-''Dose and schedule were individualized with the goal of achieving and maintaining platelets between 50 and 200 x 10<sup>9</sup>/L.''
-</div></div>
-===References===
-# '''TRA100773:''' Bussel JB, Cheng G, Saleh MN, Psaila B, Kovaleva L, Meddeb B, Kloczko J, Hassani H, Mayer B, Stone NL, Arning M, Provan D, Jenkins JM. Eltrombopag for the treatment of chronic idiopathic thrombocytopenic purpura. N Engl J Med. 2007 Nov 29;357(22):2237-47. [https://doi.org/10.1056/NEJMoa073275 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18046028 PubMed] NCT00102739
-# '''TRA100773:''' Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. [https://doi.org/10.1016/S0140-6736(09)60402-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19231632 PubMed] NCT00102739
-# '''RAISE:''' Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. [https://doi.org/10.1016/S0140-6736(10)60959-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20739054 PubMed] NCT00370331
-# '''EXTEND:''' Saleh MN, Bussel JB, Cheng G, Meyer O, Bailey CK, Arning M, Brainsky A; EXTEND Study Group. Safety and efficacy of eltrombopag for treatment of chronic immune thrombocytopenia: results of the long-term, open-label EXTEND study. Blood. 2013 Jan 17;121(3):537-45. Epub 2012 Nov 20. [http://www.bloodjournal.org/content/121/3/537.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23169778 PubMed]
-# '''PETIT2:''' Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. [https://doi.org/10.1016/S0140-6736(15)61107-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26231455 PubMed] NCT01520909
-# Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. [https://doi.org/10.1111/bjh.14380 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27734464 PubMed]
-==Fostamatinib monotherapy {{#subobject:ddb228|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:85221f|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055608/ Bussel et al. 2018 (FIT1)]
-|2014-2016
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior stable response
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055608/ Bussel et al. 2018 (FIT2)]
-|2015-2016
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior stable response
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Fostamatinib (Tavalisse)]] 100 mg PO twice per day
+*[[Bevacizumab (Avastin)]] 5 mg/kg IV once per day on days 1 & 15
-**Dose may be increased to 150 mg PO twice per day after 4 weeks if needed to achieve platelet count of at least 50
+====Supportive therapy====
-'''24-week course'''
+*PCP prophylaxis: [[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO once every Monday, Wednesday, and Friday
+**Allergic patients received alternate prophylaxis
+*VZV prophylaxis: [[Acyclovir (Zovirax)]] 400 mg PO three times per day
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''FIT1:''' Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, Windyga J, Sivcheva L, Khalafallah AA, Zaja F, Cooper N, Markovtsov V, Zayed H, Duliege AM. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921-930. Epub 2018 May 15. [https://doi.org/10.1002/ajh.25125 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055608/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29696684 PubMed] NCT02076399
+# '''DFCI 04-272:''' Chan JA, Stuart K, Earle CC, Clark JW, Bhargava P, Miksad R, Blaszkowsky L, Enzinger PC, Meyerhardt JA, Zheng H, Fuchs CS, Kulke MH. Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. J Clin Oncol. 2012 Aug 20;30(24):2963-8. Epub 2012 Jul 9. [https://doi.org/10.1200/jco.2011.40.3147 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874232/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22778320 PubMed] NCT00137774
-# '''FIT2:''' Bussel J, Arnold DM, Grossbard E, Mayer J, Treliński J, Homenda W, Hellmann A, Windyga J, Sivcheva L, Khalafallah AA, Zaja F, Cooper N, Markovtsov V, Zayed H, Duliege AM. Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: results of two phase 3, randomized, placebo-controlled trials. Am J Hematol. 2018 Jul;93(7):921-930. Epub 2018 May 15. [https://doi.org/10.1002/ajh.25125 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055608/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29696684 PubMed] NCT02076412
+==Temozolomide & Thalidomide {{#subobject:16afb7|Regimen=1}}==
-# '''Review:''' Newland A, Lee EJ, McDonald V, Bussel JB. Fostamatinib for persistent/chronic adult immune thrombocytopenia. Immunotherapy. 2018 Jan;10(1):9-25. [https://www.futuremedicine.com/doi/10.2217/imt-2017-0097?url_ver=Z39.88-2003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28967793 PubMed]
-==Mycophenolate mofetil monotherapy {{#subobject:ddb338|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:850f1f|Variant=1}}===
+===Regimen {{#subobject:ceca5a|Variant=1}}===
 {| class="wikitable" style="width: 40%; text-align:center;"
 ! style="width: 50%" |Study
 ! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1111/bjh.13622 Taylor et al. 2015]
+|[https://doi.org/10.1200/jco.2005.03.6046 Kulke et al. 2006]
-| style="background-color:#ffffbe" |Retrospective
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Immunosuppressive therapy====
+====Chemotherapy====
-*[[Mycophenolate mofetil (CellCept)]] 1 gm/day PO
+*[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 7, 15 to 21
-'''Continued indefinitely'''
+====Targeted therapy====
-</div></div>
+*[[Thalidomide (Thalomid)]] 200 mg PO once per day
-===References===
-# '''Retrospective:''' Taylor A, Neave L, Solanki S, Westwood JP, Terrinonive I, McGuckin S, Kothari J, Cooper N, Stasi R, Scully M. Mycophenolate mofetil therapy for severe immune thrombocytopenia. Br J Haematol. 2015 Nov;171(4):625-30. Epub 2015 Aug 6. [https://doi.org/10.1111/bjh.13622 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26250874 PubMed]
-==Placebo==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(08)60203-2 Kuter et al. 2008 (Amgen 20030105)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Romiplostim_monotherapy|Romiplostim]]
-| style="background-color:#d73027" |Inferior durable platelet response
-|-
-|[https://doi.org/10.1016/S0140-6736(08)60203-2 Kuter et al. 2008 (Amgen 20030212)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Romiplostim_monotherapy|Romiplostim]]
-| style="background-color:#d73027" |Inferior durable platelet response
-|-
-|[https://doi.org/10.1016/S0140-6736(09)60402-5 Bussel et al. 2009 (TRA100773)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Eltrombopag_monotherapy|Eltrombopag]]
-| style="background-color:#d73027" |Inferior RR
-|-
-|[https://doi.org/10.1016/S0140-6736(10)60959-2 Cheng et al. 2010 (RAISE-ITP)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Eltrombopag_monotherapy|Eltrombopag]]
-| style="background-color:#d73027" |Inferior RR
-|-
-|[https://doi.org/10.1016/S0140-6736(14)61495-1 Ghanima et al. 2015 (RITP)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Rituximab_monotherapy|Rituximab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of rate of treatment failure within 78 weeks
-|-
-|[https://doi.org/10.1016/S0140-6736(15)61107-2 Grainger et al. 2015 (PETIT2)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Eltrombopag_monotherapy|Eltrombopag]]
-| style="background-color:#d73027" |Inferior durable platelet response
-|-
-|[https://doi.org/10.1016/S0140-6736(16)00279-8 Tarantino et al. 2016 (Amgen 20080279)]
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Romiplostim_monotherapy|Romiplostim]]
-| style="background-color:#d73027" |Inferior durable platelet response
-|-
-|}
-''No active treatment; used as a comparator arm and here for reference purposes only. Note that RAISE should not be confused with the trial by the same name in colorectal cancer.''
-</div></div>
-===References===
-# '''Amgen 20030105:''' Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. [https://doi.org/10.1016/S0140-6736(08)60203-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18242413 PubMed] NCT00102323
-# '''Amgen 20030212:''' Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. [https://doi.org/10.1016/S0140-6736(08)60203-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18242413 PubMed] NCT00102336
-# '''TRA100773:''' Bussel JB, Provan D, Shamsi T, Cheng G, Psaila B, Kovaleva L, Salama A, Jenkins JM, Roychowdhury D, Mayer B, Stone N, Arning M. Effect of eltrombopag on platelet counts and bleeding during treatment of chronic idiopathic thrombocytopenic purpura: a randomised, double-blind, placebo-controlled trial. Lancet. 2009 Feb 21;373(9664):641-8. [https://doi.org/10.1016/S0140-6736(09)60402-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19231632 PubMed] NCT00102739
-# '''RAISE:''' Cheng G, Saleh MN, Marcher C, Vasey S, Mayer B, Aivado M, Arning M, Stone NL, Bussel JB. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study. Lancet. 2011 Jan 29;377(9763):393-402. Epub 2010 Aug 23. Erratum in: Lancet. 2011 Jan 29;377(9763):382. [https://doi.org/10.1016/S0140-6736(10)60959-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20739054 PubMed] NCT00370331
-# '''RITP:''' Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4. [https://doi.org/10.1016/S0140-6736(14)61495-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25662413 PubMed] NCT00344149
-# '''PETIT2:''' Grainger JD, Locatelli F, Chotsampancharoen T, Donyush E, Pongtanakul B, Komvilaisak P, Sosothikul D, Drelichman G, Sirachainan N, Holzhauer S, Lebedev V, Lemons R, Pospisilova D, Ramenghi U, Bussel JB, Bakshi KK, Iyengar M, Chan GW, Chagin KD, Theodore D, Marcello LM, Bailey CK. Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial. Lancet. 2015 Oct 24;386(10004):1649-58. Epub 2015 Jul 28. [https://doi.org/10.1016/S0140-6736(15)61107-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26231455 PubMed] NCT01520909
-# '''Amgen 20080279:''' Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. [https://doi.org/10.1016/S0140-6736(16)00279-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27103127 PubMed] NCT01444417
-# Yang R, Li J, Jin J, Huang M, Yu Z, Xu X, Zhang X, Hou M. Multicentre, randomised phase III study of the efficacy and safety of eltrombopag in Chinese patients with chronic immune thrombocytopenia. Br J Haematol. 2017 Jan;176(1):101-110. [https://doi.org/10.1111/bjh.14380 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27734464 PubMed]
-==Rituximab monotherapy {{#subobject:d7d211|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:128a52|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[http://www.bloodjournal.org/content/112/4/999.long Godeau et al. 2008]
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|[https://doi.org/10.1016/S0140-6736(14)61495-1 Ghanima et al. 2015 (RITP)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of rate of treatment failure within 78 weeks
-|-
-|}
-''Patients in Godeau et al. 2008 had "ITP lasting 6 or more months before inclusion; at least 1 previous treatment for ITP; and platelet count less than 30 × 10<sup>9</sup>/L at inclusion" and were candidates for splenectomy."''
-====Immunosuppressive therapy====
-*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-====Supportive therapy====
-*(per Godeau et al. 2008):
-*Patients received Streptococcus pneumoniae and Haemophilus influenzae vaccination at least 2 weeks before the first dose of [[Rituximab (Rituxan)]]
-*[[Acetaminophen (Tylenol)]] 1000 mg once per day on days 1, 8, 15, 22, prior to [[Rituximab (Rituxan)]]
-*[[Methylprednisolone (Solumedrol)]] 60 mg IV once per day on days 1, 8, 15, 22, prior to [[Rituximab (Rituxan)]]
-'''4-week course'''
-</div></div>
-===References===
-# Godeau B, Porcher R, Fain O, Lefrère F, Fenaux P, Cheze S, Vekhoff A, Chauveheid MP, Stirnemann J, Galicier L, Bourgeois E, Haiat S, Varet B, Leporrier M, Papo T, Khellaf M, Michel M, Bierling P. Rituximab efficacy and safety in adult splenectomy candidates with chronic immune thrombocytopenic purpura: results of a prospective multicenter phase 2 study. Blood. 2008 Aug 15;112(4):999-1004. [http://www.bloodjournal.org/content/112/4/999.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18463354 PubMed]
-# '''Prospective cohort:''' Patel VL, Mahévas M, Lee SY, Stasi R, Cunningham-Rundles S, Godeau B, Kanter J, Neufeld E, Taube T, Ramenghi U, Shenoy S, Ward MJ, Mihatov N, Patel VL, Bierling P, Lesser M, Cooper N, Bussel JB. Outcomes 5 years after response to rituximab therapy in children and adults with immune thrombocytopenia. Blood. 2012 Jun 21;119(25):5989-95. [http://www.bloodjournal.org/content/119/25/5989.long link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22566601 PubMed]
-# '''RITP:''' Ghanima W, Khelif A, Waage A, Michel M, Tjønnfjord GE, Romdhan NB, Kahrs J, Darne B, Holme PA; RITP study group. Rituximab as second-line treatment for adult immune thrombocytopenia (the RITP trial): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2015 Apr 25;385(9978):1653-61. Epub 2015 Feb 4.[https://doi.org/10.1016/S0140-6736(14)61495-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25662413 PubMed] NCT00344149
-==Romiplostim monotherapy {{#subobject:a6df46|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8b8d3b|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |Comparator
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1016/S0140-6736(08)60203-2 Kuter et al. 2008 (Amgen 20030105)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior durable platelet response
-|-
-|[https://doi.org/10.1016/S0140-6736(08)60203-2 Kuter et al. 2008 (Amgen 20030212)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior durable platelet response
-|-
-|[https://doi.org/10.1016/S0140-6736(16)00279-8 Tarantino et al. 2016 (Amgen 20080279)]
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior durable platelet response
-|-
-|}
-''Patients in Amgen 20030105 had undergone splenectomy. Patients in Amgen 20080279 were younger than 18 years old at time of study entry; see paper for details on dose titration.''
-====Growth factor therapy====
-*[[Romiplostim (Nplate)]] 1 mcg/kg SC once per day on days 1, 8, 15, 22
 '''28-day cycles'''
 </div></div>
 ===References===
-# '''Amgen 20030105:''' Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. [https://doi.org/10.1016/S0140-6736(08)60203-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18242413 PubMed] NCT00102323
+# Kulke MH, Stuart K, Enzinger PC, Ryan DP, Clark JW, Muzikansky A, Vincitore M, Michelini A, Fuchs CS. Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol. 2006 Jan 20;24(3):401-6. [https://doi.org/10.1200/jco.2005.03.6046 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16421420 PubMed]
-# '''Amgen 20030212:''' Kuter DJ, Bussel JB, Lyons RM, Pullarkat V, Gernsheimer TB, Senecal FM, Aledort LM, George JN, Kessler CM, Sanz MA, Liebman HA, Slovick FT, de Wolf JT, Bourgeois E, Guthrie TH Jr, Newland A, Wasser JS, Hamburg SI, Grande C, Lefrère F, Lichtin AE, Tarantino MD, Terebelo HR, Viallard JF, Cuevas FJ, Go RS, Henry DH, Redner RL, Rice L, Schipperus MR, Guo DM, Nichol JL. Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomised controlled trial. Lancet. 2008 Feb 2;371(9610):395-403. [https://doi.org/10.1016/S0140-6736(08)60203-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18242413 PubMed] NCT00102336
+[[Category:Pancreatic NET regimens]]
-# '''Amgen 20080279:''' Tarantino MD, Bussel JB, Blanchette VS, Despotovic J, Bennett C, Raj A, Williams B, Beam D, Morales J, Rose MJ, Carpenter N, Nie K, Eisen M. Romiplostim in children with immune thrombocytopenia: a phase 3, randomised, double-blind, placebo-controlled study. Lancet. 2016 Jul 2;388(10039):45-54. Epub 2016 Apr 18. [https://doi.org/10.1016/S0140-6736(16)00279-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27103127 PubMed] NCT01444417
-== Vinblastine-loaded platelets ==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen ===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 33%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
-|-
-|[https://doi.org/10.1056/NEJM197805182982001 Ahn et al. 1978]
-| style="background-color:#ffffbe" |Phase 1
-|CR in 6 of 11 patients
-|}
-=== Reference ===
-# '''Phase 1:''' Ahn YS, Byrnes JJ, Harrington WJ, Cayer ML, Smith DS, Brunskill DE, Pall LM. New England Journal of Medicine. 1978; 298:1101-1107. [https://doi.org/10.1056/NEJM197805182982001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/565464 PubMed]
-[[Category:Immune thrombocytopenia regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Autoimmune hematologic conditions]]
+[[Category:Endocrine cancers]]
-[[Category:Bleeding disorders]]
+[[Category:Gastrointestinal cancers]]
-[[Category:Cytopenias]]
-[[Category:Clinical pharmacology]]

Difference between revisions of "Staging page"

Revision as of 12:58, 17 October 2022

Guidelines

ESMO

Older

NANETS

NCCN

All lines of therapy

Capecitabine & Temozolomide

Regimen

Chemotherapy

Supportive therapy

References

Doxorubicin & Streptozocin

Regimen

Chemotherapy

References

Everolimus monotherapy

Regimen

Targeted therapy

References

Everolimus & Octreotide

Regimen variant #1

Targeted therapy

Endocrine therapy

Regimen variant #2

Targeted therapy

Endocrine therapy

References

FAS

Regimen

Chemotherapy

References

Fluorouracil & Streptozocin

Regimen

Chemotherapy

References

Lanreotide Depot/Autogel monotherapy

Regimen

Endocrine therapy

References

Lanreotide & Interferon alfa-2b

Regimen

Endocrine therapy

Immunotherapy

References

Octreotide monotherapy

Regimen

Endocrine therapy

References

Octreotide LAR monotherapy

Regimen

Endocrine therapy

References

Octreotide & Interferon alfa

Regimen

Endocrine therapy

Immunotherapy

References

Lutetium Lu 177 dotatate & Octreotide LAR

Regimen

Endocrine therapy

Radioconjugate therapy

Supportive therapy

References

Sunitinib monotherapy

Regimen

Targeted therapy

References

Temozolomide monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Temozolomide & Bevacizumab

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References