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| | Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]]. | | Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]]. |
| | + | |
| | + | <big>'''This page is now exclusively focused on those tumors commonly called carcinoids, which may or may not be associated with the carcinoid syndrome; there are now separate pages for [[pancreatic NET]] and other endocrine cancers. Neuroendocrine tumors of unknown primary and poorly differentiated (high-grade) neuroendocrine tumors are usually treated with a [[small cell lung cancer]] regimen.'''</big> |
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| | {{TOC limit|limit=3}} | | {{TOC limit|limit=3}} |
| − |
| |
| | =Guidelines= | | =Guidelines= |
| | ==ESMO== | | ==ESMO== |
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| | *[https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf NCCN Guidelines - Neuroendocrine Tumors] | | *[https://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf NCCN Guidelines - Neuroendocrine Tumors] |
| | | | |
| − | =Adrenal gland tumors, adrenocortical carcinoma - adjuvant therapy= | + | =All lines of therapy= |
| − | | |
| − | ==Mitotane monotherapy {{#subobject:ef7e79|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | '''There is limited and controversial clinical trial information about adjuvant mitotane use. See the references for additional case series and expert recommendation articles.'''
| |
| − | | |
| − | ===Regimen #1 {{#subobject:45870b|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://erc.endocrinology-journals.org/content/17/1/265.long Wängberg et al. 2010]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ''Patients started on adjuvant mitotane within 4 weeks of their surgical resection.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] 2000 mg PO per day (frequency not specified, such as whether the total daily dose was divided into a few doses throughout the day); within the first 2 to 3 months, dose was adjusted to achieve a target therapeutic drug level of 14 to 20 mg/L
| |
| − | | |
| − | '''2 to 3-year course'''
| |
| − | | |
| − | ===Regimen #2 {{#subobject:67a83e|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968906/ Haak et al. 1994]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ''Haak et al. 1994 concluded that "mitotane treatment in adrenocortical carcinoma is effective only when high
| |
| − | serum levels [trough of at least 14 mg/L] can be achieved."''
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] 1000 to 2000 mg PO QID (total dose per day: 4000 to 8000 mg), with target mitotane trough of above 14 mg/L
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Hydrocortisone (Cortef)]] 30 to 120 mg per day or [[Fludrocortisone (Florinef)]] 0.1 to 0.4 mg per day
| |
| − | *[[Metoclopramide (Reglan)]] prn "gastrointestinal side-effects"
| |
| − | *[[Loperamide (Imodium)]] prn "gastrointestinal side-effects"
| |
| − | | |
| − | '''2-year course "if resection was judged to be complete or for 1 year after apparent disappearance of the tumour"'''
| |
| − | | |
| − | ===References===
| |
| − | # Vassilopoulou-Sellin R, Guinee VF, Klein MJ, Taylor SH, Hess KR, Schultz PN, Samaan NA. Impact of adjuvant mitotane on the clinical course of patients with adrenocortical cancer. Cancer. 1993 May 15;71(10):3119-23. [http://onlinelibrary.wiley.com/doi/10.1002/1097-0142%2819930515%2971:10%3C3119::AID-CNCR2820711037%3E3.0.CO;2-8/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8490842 PubMed]
| |
| − | # Haak HR, Hermans J, van de Velde CJ, Lentjes EG, Goslings BM, Fleuren GJ, Krans HM. Optimal treatment of adrenocortical carcinoma with mitotane: results in a consecutive series of 96 patients. Br J Cancer. 1994 May;69(5):947-51. '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1968906/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/8180029 PubMed] content property of [http://hemonc.org HemOnc.org]
| |
| − | # Terzolo M, Angeli A, Fassnacht M, Daffara F, Tauchmanova L, Conton PA, Rossetto R, Buci L, Sperone P, Grossrubatscher E, Reimondo G, Bollito E, Papotti M, Saeger W, Hahner S, Koschker AC, Arvat E, Ambrosi B, Loli P, Lombardi G, Mannelli M, Bruzzi P, Mantero F, Allolio B, Dogliotti L, Berruti A. Adjuvant mitotane treatment for adrenocortical carcinoma. N Engl J Med. 2007 Jun 7;356(23):2372-80. [http://www.nejm.org/doi/full/10.1056/NEJMoa063360 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17554118 PubMed]
| |
| − | # Veytsman I, Nieman L, Fojo T. Management of endocrine manifestations and the use of mitotane as a chemotherapeutic agent for adrenocortical carcinoma. J Clin Oncol. 2009 Sep 20;27(27):4619-29. Epub 2009 Aug 10. [http://jco.ascopubs.org/content/27/27/4619.full link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754909/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19667279 PubMed]
| |
| − | # Wängberg B, Khorram-Manesh A, Jansson S, Nilsson B, Nilsson O, Jakobsson CE, Lindstedt S, Odén A, Ahlman H. The long-term survival in adrenocortical carcinoma with active surgical management and use of monitored mitotane. Endocr Relat Cancer. 2010 Feb 18;17(1):265-72. Print 2010 Mar. [http://erc.endocrinology-journals.org/content/17/1/265.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20026647 PubMed]
| |
| − | | |
| − | ==Mitotane & Streptozocin {{#subobject:942057|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:3a7fbd|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://annonc.oxfordjournals.org/content/11/10/1281.long Khan et al. 2010]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ====Induction course====
| |
| − | *[[Streptozocin (Zanosar)]] 1000 mg IV once per day on days 1 to 5
| |
| − | | |
| − | '''5-day course, followed by main regimen'''
| |
| − | | |
| − | ====Main regimen====
| |
| − | *[[Mitotane (Lysodren)]] 1000 to 4000 mg/day PO; daily dose is taken in 2 to 3 divided doses per day
| |
| − | *[[Streptozocin (Zanosar)]] 2000 mg IV once per day on days 1 to 5
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Antiemesis|5-HT3 antagonists]] prior to streptozocin
| |
| − | *Hydrocortisone (Cortef) 25 to 100 mg/day
| |
| − | | |
| − | '''21-day cycles; duration of therapy not clearly specified'''
| |
| − | | |
| − | ===References===
| |
| − | # Khan TS, Imam H, Juhlin C, Skogseid B, Gröndal S, Tibblin S, Wilander E, Oberg K, Eriksson B. Streptozocin and o,p'DDD in the treatment of adrenocortical cancer patients: long-term survival in its adjuvant use. Ann Oncol. 2000 Oct;11(10):1281-7. [http://annonc.oxfordjournals.org/content/11/10/1281.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11106117 PubMed]
| |
| − | | |
| − | =Adrenal gland tumors, adrenocortical carcinoma - recurrent, locally advanced, or metastatic disease=
| |
| − | | |
| − | ==Mitotane monotherapy {{#subobject:e99e96|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:17527c|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754909/ Veytsman et al. 2009]
| |
| − | |style="background-color:#ff0000"|Review
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] 1000 to 2000 mg PO per day (frequency not specified), then increase dose by 1000 to 2000 mg every 1 to 2 weeks to the maximum tolerated dose, not to exceed 6000 mg ("never greater than 6 to 10 g/d").
| |
| − | **Target mitotane drug level is 10 to 14 mg/L.
| |
| − | | |
| − | ===References===
| |
| − | # '''Review:''' Veytsman I, Nieman L, Fojo T. Management of endocrine manifestations and the use of mitotane as a chemotherapeutic agent for adrenocortical carcinoma. J Clin Oncol. 2009 Sep 20;27(27):4619-29. Epub 2009 Aug 10. [http://jco.ascopubs.org/content/27/27/4619.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754909/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19667279 PubMed]
| |
| − | | |
| − | ==Mitotane & EDP {{#subobject:8a7788|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | EDP: '''<u>E</u>'''toposide, '''<u>D</u>'''oxorubicin, '''<u>P</u>'''latinol (Cisplatin)
| |
| − | | |
| − | ===Regimen #1 {{#subobject:ded16a|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1200966 Fassnacht et al. 2012 (FIRM-ACT)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[Neuroendocrine_tumors#Mitotane_.26_Streptozocin_2|Mitotane & Streptozocin]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ''Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] on days 1 to 28, with target mitotane trough of 14 to 20 mg/L (initial dose and frequency not specified)
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 2 to 4
| |
| − | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV once on day 1
| |
| − | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 3 & 4
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[:Category:Steroids|Glucocorticoid]] replacement was recommended in all patients except those with persistent Cushing's syndrome.
| |
| − | | |
| − | '''28-day cycles'''
| |
| − | | |
| − | ===Regimen #2 {{#subobject:2dd6a8|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://erc.endocrinology-journals.org/content/12/3/657.long Berruti et al. 2005]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] 1000 mg PO per day (frequency not specified, such as whether the total daily dose was divided into a few doses throughout the day) on days 1 to 28; then dose is increased as tolerated up to 4000 mg/day or maximum tolerated dose
| |
| − | *[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 5 to 7
| |
| − | *[[Doxorubicin (Adriamycin)]] 20 mg/m<sup>2</sup> IV once per day on days 1 & 8
| |
| − | *[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV once per day on days 2 & 9
| |
| − | | |
| − | '''28-day cycle for up to 6 cycles, given until progression of disease, unacceptable toxicity, or patient refusal'''
| |
| − | | |
| − | ===References===
| |
| − | # Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, Carnaghi C, Casali P, Porpiglia F, Mantero F, Reimondo G, Angeli A, Dogliotti L. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. [http://erc.endocrinology-journals.org/content/12/3/657.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16172198 PubMed]
| |
| − | # Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardière C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Müller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. Epub 2012 May 2. [http://www.nejm.org/doi/full/10.1056/NEJMoa1200966 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22551107 PubMed]
| |
| − | | |
| − | ==Mitotane & Streptozocin {{#subobject:bd8397|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:d34072|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1200966 Fassnacht et al. 2012 (FIRM-ACT)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[Neuroendocrine_tumors#Mitotane_.26_EDP|Mitotane & EDP]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ''Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.''
| |
| − | ====Chemotherapy====
| |
| − | *[[Mitotane (Lysodren)]] PO on days 1 to 21 (initial dose and frequency not specified)
| |
| − | **Target mitotane trough of 14 to 20 mg/L
| |
| − | *[[Streptozocin (Zanosar)]] as follows:
| |
| − | **Cycle 1: 1000 mg IV once per day on days 1 to 5
| |
| − | **Cycle 2 onwards: 2000 mg IV once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[:Category:Steroids|Glucocorticoid]] replacement was recommended in all patients except those with persistent Cushing's syndrome.
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardière C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Müller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. Epub 2012 May 2. [http://www.nejm.org/doi/full/10.1056/NEJMoa1200966 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22551107 PubMed]
| |
| − | | |
| − | =Carcinoid tumors=
| |
| | | | |
| | ==Everolimus monotherapy {{#subobject:99989f|Regimen=1}}== | | ==Everolimus monotherapy {{#subobject:99989f|Regimen=1}}== |
| Line 571: |
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| | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17505000 PubMed] | | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17505000 PubMed] |
| | | | |
| − | =Neuroendocrine tumors of unknown primary, poorly differentiated (high-grade) neuroendocrine tumors=
| + | [[Category:Neuroendocrine tumors regimens]] |
| − | The NCCN Guidelines, Neuroendocrine tumors version 1.2013, suggests that these are treated with a [[small cell lung cancer]] regimen.
| |
| − | | |
| − | =Pancreatic neuroendocrine islet cell tumors=
| |
| − | | |
| − | ==Everolimus monotherapy {{#subobject:78dff1|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:5ea369|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ Yao et al. 2010]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |style="background-color:#d3d3d3"|
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ Yao et al. 2011 (RADIANT-3)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Placebo_2|Placebo]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Everolimus (Afinitor)]] 10 mg PO once per day
| |
| − | | |
| − | '''Given until progression of disease, unacceptable toxicity, drug interruption of 3 weeks or longer, or withdrawal of consent'''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://jco.ascopubs.org/content/28/1/69.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19933912 PubMed]
| |
| − | # 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1009290 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21306238 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://www.ncbi.nlm.nih.gov/pubmed/23436795 PubMed]
| |
| − | | |
| − | ==FAS {{#subobject:66b05e|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | FAS: '''<u>F</u>'''luorouracil, '''<u>A</u>'''driamycin (Doxorubicin), '''<u>S</u>'''treptozocin
| |
| − | | |
| − | ===Regimen {{#subobject:de76a2|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/22/23/4762.long Kouvaraki et al. 2004]
| |
| − | |style="background-color:#ff0000"|Retrospective
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
| |
| − | *[[Doxorubicin (Adriamycin)]] 40 mg/m<sup>2</sup> IV bolus once on day 1
| |
| − | *[[Streptozocin (Zanosar)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
| |
| − | | |
| − | '''28-day cycles, given until progression of disease, unacceptable toxicity, or patient intolerance'''
| |
| − | | |
| − | ===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. [http://jco.ascopubs.org/content/22/23/4762.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15570077 PubMed]
| |
| − | | |
| − | ==Lanreotide Depot/Autogel monotherapy {{#subobject:8bca3a|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:a9ee08|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1316158 Caplin et al. 2014 (CLARINET)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Placebo_2|Placebo]]
| |
| − | |style="background-color:#1a9850"|Superior PFS
| |
| − | |-
| |
| − | |}
| |
| − | ====Endocrine therapy====
| |
| − | *[[Lanreotide (Somatuline) | Lanreotide (Somatuline) Depot/Autogel]] 120 mg deep subcutaneous injection once on day 1
| |
| − | | |
| − | '''28-day cycle for 96 weeks (CLARINET), until progression of disease, or unacceptable toxicity'''
| |
| − | | |
| − | ''Patients in NET729 (unpublished) could be treated for up to 8 years.''
| |
| − | | |
| − | ===References===
| |
| − | # Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlácková 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1316158 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25014687 PubMed]
| |
| − | # [http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022074s011lbl.pdf Lanreotide (Somatuline) package insert]
| |
| − | # NIHR (National Institute for Health Research) Horizon Scanning Centre, School of Health & Population Sciences, University of Birmingham. [http://www.hsc.nihr.ac.uk/files/.../2695.647d3d17.Lanreotide_Nov14.pdf Lanreotide for unresectable, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours – first line]
| |
| − | # ClinicalTrials.gov: [https://clinicaltrials.gov/ct2/show/NCT00842348 Study of Lanreotide Autogel 120mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour (NET729)]
| |
| − | | |
| − | ==Lanreotide & Interferon alfa {{#subobject:9c5a59|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:652f4d|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 Fjällskog et al. 2002]
| |
| − | |style="background-color:#ff0000"|Pilot, <20 pts
| |
| − | |-
| |
| − | |}
| |
| − | ''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 & Immunotherapy====
| |
| − | *[[Lanreotide (Somatuline)]] 3 mg SC BID
| |
| − | *[[Interferon alfa-2b (Intron-A)]] 3 to 5 million units SC given once per day, 3 to 7 days per week (total of 9 to 25 million 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. [http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12025889 PubMed]
| |
| − | | |
| − | ==Octreotide monotherapy {{#subobject:665a8b|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen {{#subobject:cd8cf6|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://annonc.oxfordjournals.org/content/15/6/966.long Oberg et al. 2004]
| |
| − | |style="background-color:#ff0000"|Consensus guideline
| |
| − | |-
| |
| − | |}
| |
| − | ====Endocrine therapy====
| |
| − | *[[Octreotide (Sandostatin)]] 0.1 to 0.5 mg SC given 2 to 4 times per day, with dose increased by doubling the dose every 3 to 4 days as needed to control symptoms
| |
| − | **"A reasonable starting dose is" 0.15 mg SC TID
| |
| − | | |
| − | '''Treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms'''
| |
| − | | |
| − | ===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. [http://www.sciencedirect.com/science/article/pii/S0039610905701419 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/11459269 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. [http://annonc.oxfordjournals.org/content/15/6/966.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15151956 PubMed]
| |
| − | | |
| − | ==Octreotide LAR monotherapy {{#subobject:e356ea|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen #1 {{#subobject:200e99|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://annonc.oxfordjournals.org/content/15/6/966.long Oberg et al. 2004]
| |
| − | |style="background-color:#ff0000"|Consensus guideline
| |
| − | |-
| |
| − | |}
| |
| − | ====Endocrine therapy====
| |
| − | *[[Octreotide LAR (Sandostatin LAR)]] 20 to 30 mg IM once on day 1, with potentially higher doses if needed for symptom control
| |
| − | **"As a general rule, if the total [octreotide] IR dose is 200 to 600 mcg/day, LAR 20 mg should be tried, and if total IR dose is 750 to 1500 mcg/day, LAR 30 mg should be tried."
| |
| − | *[[Octreotide (Sandostatin)]] (dose not specified) SC as needed for additional symptom control
| |
| − | | |
| − | '''28-day cycles; treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms'''
| |
| − | | |
| − | ===Regimen #2 {{#subobject:f0bc1b|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/27/28/4656.long Rinke et al. 2009 (PROMID)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Placebo_2|Placebo]]
| |
| − | |style="background-color:#1a9850"|Superior TTP
| |
| − | |-
| |
| − | |}
| |
| − | ====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, given until progression of disease'''
| |
| − | | |
| − | ===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. [http://annonc.oxfordjournals.org/content/15/6/966.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15151956 PubMed]
| |
| − | # 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. [http://jco.ascopubs.org/content/27/28/4656.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19704057 PubMed]
| |
| − | | |
| − | ==Octreotide & Everolimus {{#subobject:d6b3eb|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | ===Regimen #1 {{#subobject:b0f62f|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ Yao et al. 2010]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ''Patients in Yao et al. 2010 who received this regimen had already been receiving octreotide LAR for at least 3 months before participating in the study.''
| |
| − | ====Endocrine & Chemotherapy====
| |
| − | *[[Octreotide LAR (Sandostatin LAR)]] ≤30 mg (whatever their prestudy dose was) IM once every 28 days
| |
| − | *[[Everolimus (Afinitor)]] 10 mg PO once per day
| |
| − | | |
| − | '''Given until progression of disease, unacceptable toxicity, drug interruption of 3 weeks or longer, or withdrawal of consent'''
| |
| − | | |
| − | ===Regimen #2 {{#subobject:f82bb5|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ Yao et al. 2008]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ''Note: Everolimus "dose of 10 mg was associated with superior PFS...however, the study was not prospectively powered for these comparisons. These analyses should be considered exploratory."''
| |
| − | ====Endocrine & Chemotherapy====
| |
| − | *[[Octreotide LAR (Sandostatin LAR)]] 30 mg IM once on day 1
| |
| − | *[[Everolimus (Afinitor)]] 5 or 10 mg PO once per day on days 1 to 28
| |
| − | | |
| − | '''28-day cycle for up to 12 cycles or until progression of disease, though treatment could be continued beyond this period if thought by the treating physician to be beneficial'''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://jco.ascopubs.org/content/26/26/4311.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653122/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18779618 PubMed]
| |
| − | # 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. [http://jco.ascopubs.org/content/28/1/69.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295034/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19933912 PubMed]
| |
| − | | |
| − | ==Octreotide & Interferon alfa {{#subobject:1cf4c5|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:cbf5c4|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://link.springer.com/article/10.1385%2FMO%3A19%3A1%3A35 Fjällskog et al. 2002]
| |
| − | |style="background-color:#ff0000"|Pilot, <20 pts
| |
| − | |-
| |
| − | |}
| |
| − | ''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 & Immunotherapy====
| |
| − | *[[Octreotide (Sandostatin)]] 0.05 to 0.5 mg SC given 2 to 3 times per day
| |
| − | *[[Interferon alfa-2b (Intron-A)]] 3 to 5 million units SC given once per day, 3 to 7 days per week (total of 9 to 25 million 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. [http://informahealthcare.com/doi/abs/10.3109/02841869309083916 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7686765 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://www.ncbi.nlm.nih.gov/pubmed/12025889 PubMed]
| |
| − | # Fazio N, de Braud F, Delle Fave G, Oberg K. Interferon-alpha and somatostatin analog in patients with gastroenteropancreatic neuroendocrine carcinoma: single agent or combination? Ann Oncol. 2007 Jan;18(1):13-9. Epub 2006 Jun 23. [http://annonc.oxfordjournals.org/content/18/1/13.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16798833 PubMed]
| |
| − | | |
| − | ==Placebo==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/27/28/4656.long Rinke et al. 2009 (PROMID)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Octreotide_LAR_monotherapy_2|Octreotide LAR]]
| |
| − | |style="background-color:#d73027"|Inferior TTP
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1003825 Raymond et al. 2011]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Sunitinib_monotherapy|Sunitinib]]
| |
| − | |style="background-color:#fc8d59"|Seems to have inferior OS
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ Yao et al. 2011 (RADIANT-3)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Everolimus_monotherapy_2|Everolimus]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1316158 Caplin et al. 2014 (CLARINET)]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Lanreotide_Depot.2FAutogel_monotherapy|Lanreotide]]
| |
| − | |style="background-color:#d73027"|Inferior PFS
| |
| − | |-
| |
| − | |}
| |
| − | | |
| − | ''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://jco.ascopubs.org/content/27/28/4656.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19704057 PubMed]
| |
| − | # 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1003825 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21306237 PubMed]
| |
| − | # 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1009290 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208619/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21306238 PubMed]
| |
| − | # Caplin ME, Pavel M, Cwikla JB, Phan AT, Raderer M, Sedlácková 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1316158 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25014687 PubMed]
| |
| − | | |
| − | ==Streptozocin & Doxorubicin {{#subobject:5c625d|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:a9c7ed|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJM199202203260804 Moertel et al. 1992]
| |
| − | |rowspan=2 style="background-color:#00cd00"|Phase III
| |
| − | |Chlorozotocin
| |
| − | |style="background-color:#1a9850"|Superior OS
| |
| − | |-
| |
| − | |[[Neuroendocrine_tumors#Streptozocin_.26_Fluorouracil|Streptozocin & Fluorouracil]]
| |
| − | |style="background-color:#1a9850"|Superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Streptozocin (Zanosar)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once per day on days 1 & 22
| |
| − | | |
| − | '''42-day cycles, given until progression of disease'''
| |
| − | | |
| − | ===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. [http://www.nejm.org/doi/full/10.1056/NEJM199202203260804 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1310159 PubMed]
| |
| − | | |
| − | ==Streptozocin & Fluorouracil {{#subobject:6f7b84|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:e45011|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJM199202203260804 Moertel et al. 1992]
| |
| − | |rowspan=2 style="background-color:#00cd00"|Phase III
| |
| − | |Chlorozotocin
| |
| − | |style="background-color:#ffffbf"|Seems not superior
| |
| − | |-
| |
| − | |[[Neuroendocrine_tumors#Streptozocin_.26_Doxorubicin|Streptozocin & Doxorubicin]]
| |
| − | |style="background-color:#d73027"|Inferior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Streptozocin (Zanosar)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
| |
| − | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
| |
| − | | |
| − | '''42-day cycles, given until progression of disease'''
| |
| − | | |
| − | ===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. [http://www.nejm.org/doi/full/10.1056/NEJM199202203260804 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1310159 PubMed]
| |
| − | | |
| − | ==Sunitinib monotherapy {{#subobject:ee13d2|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:80d0ef|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |'''Comparator'''
| |
| − | |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
| |
| − | |-
| |
| − | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1003825 Raymond et al. 2011]
| |
| − | |style="background-color:#00cd00"|Phase III
| |
| − | |[[#Placebo_2|Placebo]]
| |
| − | |style="background-color:#91cf60"|Seems to have superior OS
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Sunitinib (Sutent)]] 37.5 mg PO once per day
| |
| − | | |
| − | '''Given until progression of disease, unacceptable toxicity, or patient death'''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1003825 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21306237 PubMed]
| |
| − | | |
| − | ==Temozolomide monotherapy {{#subobject:69ae1c|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:6aac4c|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://clincancerres.aacrjournals.org/content/13/10/2986.long Ekeblad et al. 2007]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Temozolomide (Temodar)]] as follows:
| |
| − | **Cycle 1: 100 or 150 mg/m<sup>2</sup> PO once per day on days 1 to 5
| |
| − | **Cycle 2 onwards: increased as tolerated up to 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Tropisetron (Navoban)]] (dose/route/schedule not specified) routinely used as an antiemetic
| |
| − | | |
| − | '''28-day cycles, given until progression of disease or unacceptable toxicity'''
| |
| − | | |
| − | ===References===
| |
| − | # 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 verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17505000 PubMed]
| |
| − | | |
| − | ==Temozolomide & Bevacizumab {{#subobject:ce7fe6|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:be3718|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874232/ Chan et al. 2012]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 7, 15 to 21
| |
| − | *[[Bevacizumab (Avastin)]] 5 mg/kg IV once per day on days 1 & 15
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Trimethoprim/Sulfamethoxazole (Bactrim DS)]] 160/800 mg PO once every Monday, Wednesday, and Friday; allergic patients received alternate Pneumocystis carinii (PCP) prophylaxis
| |
| − | *[[Acyclovir (Zovirax)]] 400 mg PO TID as prophylaxis against varicella zoster
| |
| − | | |
| − | '''28-day cycles, given until progression of disease or unacceptable toxicity'''
| |
| − | | |
| − | ===References===
| |
| − | # 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. [http://jco.ascopubs.org/content/30/24/2963.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874232/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22778320 PubMed]
| |
| − | | |
| − | ==Temozolomide & Capecitabine {{#subobject:738284|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:fc2dd9|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665634/ Strosberg et al. 2011]
| |
| − | |style="background-color:#ff0000"|Retrospective
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day at bedtime on days 10 to 14
| |
| − | *[[Capecitabine (Xeloda)]] 750 mg/m<sup>2</sup> PO BID on days 1 to 14
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *[[Ondansetron (Zofran)]] 8 mg (route not specified) prior to each dose of [[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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25425/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665634/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/20824724 PubMed]
| |
| − | | |
| − | ==Temozolomide & Thalidomide {{#subobject:16afb7|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | | |
| − | ===Regimen {{#subobject:ceca5a|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://jco.ascopubs.org/content/24/3/401.long Kulke et al. 2006]
| |
| − | |style="background-color:#eeee00"|Phase II
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Temozolomide (Temodar)]] 150 mg/m<sup>2</sup> PO once per day on days 1 to 7, 15 to 21
| |
| − | *[[Thalidomide (Thalomid)]] 200 mg PO once per day
| |
| − | | |
| − | '''28-day cycles, given until progression of disease or unacceptable toxicity'''
| |
| − | | |
| − | ===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. [http://jco.ascopubs.org/content/24/3/401.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16421420 PubMed]
| |
| − | | |
| − | =Pheochromocytoma=
| |
| − | | |
| − | ==CVD {{#subobject:6ff914|Regimen=1}}==
| |
| − | {| class="wikitable" style="float:right; margin-left: 5px;"
| |
| − | |-
| |
| − | |[[#top|back to top]]
| |
| − | |}
| |
| − | CVD: '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>D</u>'''acarbazine
| |
| − | | |
| − | ===Regimen {{#subobject:5998d1|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://annals.org/article.aspx?articleid=702515 Averbuch et al. 1988]
| |
| − | |style="background-color:#ff0000"|Pilot, <20 pts
| |
| − | |-
| |
| − | |}
| |
| − | ====Chemotherapy====
| |
| − | *[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
| |
| − | *[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> IV once on day 1
| |
| − | *[[Dacarbazine (DTIC)]] 600 mg/m<sup>2</sup> IV once per day on days 1 & 2
| |
| − | | |
| − | '''21-day cycles'''
| |
| − | | |
| − | ===References===
| |
| − | # Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med. 1988 Aug 15;109(4):267-73. [http://annals.org/article.aspx?articleid=702515 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/3395037 PubMed]
| |
| − | | |
| − | ==<sup>131</sup>I-Metaiodobenzylguanidine (<sup>131</sup>I-MIBG)==
| |
| − | Also known as m-[131I]iodobenzylguanidine ([131I]MIBG).
| |
| − | | |
| − | ===Regimen #1 {{#subobject:f474b2|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11518/full Rose et al. 2003]
| |
| − | |style="background-color:#ff0000"|Pilot, <20 pts
| |
| − | |-
| |
| − | |}
| |
| − | ''Patients underwent stem cell harvest prior to treatment in case autologous stem cell infusion was needed.''
| |
| − | ====Radiotherapy====
| |
| − | *<sup>131</sup>I-Metaiodobenzylguanidine (<sup>131</sup>I-MIBG) 12 to 18 mCi/kg (maximum single dose of 850 mCi) IV over 2 hours once on day 1
| |
| − | | |
| − | ====Supportive medications====
| |
| − | *Intravenous fluids started 12 hours before 131I-MIBG administration.
| |
| − | *Potassium iodide (KI) 6 mg/kg PO once at least 2 hours prior to 131I-MIBG, then potassium iodide (KI) 0.88 mg/kg PO Q4H x 7 days, then potassium iodide (KI) 1 mg/kg PO (frequency not specified) "for 45 days after the infusion."
| |
| − | *Potassium perchlorate 8 mg/kg once at least 2 hours prior to 131I-MIBG, then potassium perchlorate 2 mg/kg PO Q6H x 5 days.
| |
| − | | |
| − | '''"Repeat 131I-MIBG treatments were administered on a case-by-case basis in an effort to improve the overall response"'''
| |
| − | | |
| − | ===Regimen #2 {{#subobject:53e027|Variant=1}}===
| |
| − | {| border="1" style="text-align:center;" !align="left"
| |
| − | |'''Study'''
| |
| − | |[[Levels_of_Evidence#Evidence|'''Evidence''']]
| |
| − | |-
| |
| − | |[http://jcem.endojournals.org/content/72/2/455.long Krempf et al. 1991]
| |
| − | |style="background-color:#ff0000"|Pilot, <20 pts
| |
| − | |-
| |
| − | |}
| |
| − | ====Radiotherapy====
| |
| − | *m-[131I]iodobenzylguanidine ([131I]MIBG) 740 megabequerel/mg every 3 months
| |
| − | | |
| − | ===References===
| |
| − | # Krempf M, Lumbroso J, Mornex R, Brendel AJ, Wemeau JL, Delisle MJ, Aubert B, Carpentier P, Fleury-Goyon MC, Gibold C et al. Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma. J Clin Endocrinol Metab. 1991 Feb;72(2):455-61. [http://jcem.endojournals.org/content/72/2/455.long link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1991814 PubMed]
| |
| − | # Rose B, Matthay KK, Price D, Huberty J, Klencke B, Norton JA, Fitzgerald PA. High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma. Cancer. 2003 Jul 15;98(2):239-48. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11518/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12872341 PubMed]
| |
| − | | |
| − | [[Category:Adrenocortical carcinoma regimens]]
| |
| − | [[Category:Carcinoid tumor regimens]]
| |
| − | [[Category:Pancreatic NET regimens]]
| |
| − | [[Category:Pheochromocytoma regimens]]
| |
| | [[Category:Disease-specific pages]] | | [[Category:Disease-specific pages]] |
| | [[Category:Endocrine cancers]] | | [[Category:Endocrine cancers]] |