Difference between revisions of "Neuroendocrine tumor"
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− | EDP: '''<u>E</u>'''toposide, '''<u>D</u>'''oxorubicin, '''<u>P</u>'''latinol | + | EDP: '''<u>E</u>'''toposide, '''<u>D</u>'''oxorubicin, '''<u>P</u>'''latinol (Cisplatin) |
− | ===Regimen #1 | + | ===Regimen #1 {{#subobject:ded16a|Variant=1}}=== |
− | + | {| border="1" style="text-align:center;" !align="left" | |
− | <span | + | |'''Study''' |
+ | |[[Levels_of_Evidence#Evidence|'''Evidence''']] | ||
+ | |'''Comparator''' | ||
+ | |- | ||
+ | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1200966 Fassnacht et al. 2012 (FIRM-ACT)] | ||
+ | |<span | ||
style="background:#00CD00; | style="background:#00CD00; | ||
padding:3px 6px 3px 6px; | padding:3px 6px 3px 6px; | ||
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border-width:2px; | border-width:2px; | ||
border-style:solid;">Phase III</span> | border-style:solid;">Phase III</span> | ||
+ | |[[Neuroendocrine_tumors#Mitotane_.26_Streptozocin_2|Mitotane & Streptozocin]] | ||
+ | |- | ||
+ | |} | ||
''Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.'' | ''Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.'' | ||
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*[[Doxorubicin (Adriamycin)]] 40 mg/m2 IV once on day 1 | *[[Doxorubicin (Adriamycin)]] 40 mg/m2 IV once on day 1 | ||
*[[Cisplatin (Platinol)]] 40 mg/m2 IV once per day on days 3 & 4 | *[[Cisplatin (Platinol)]] 40 mg/m2 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''' | '''28-day cycles''' | ||
− | + | ===Regimen #2 {{#subobject:2dd6a8|Variant=1}}=== | |
− | + | {| border="1" style="text-align:center;" !align="left" | |
− | + | |'''Study''' | |
− | ===Regimen #2 | + | |[[Levels_of_Evidence#Evidence|'''Evidence''']] |
− | + | |- | |
− | <span | + | |[http://erc.endocrinology-journals.org/content/12/3/657.long Berruti et al. 2005] |
+ | |<span | ||
style="background:#EEEE00; | style="background:#EEEE00; | ||
padding:3px 6px 3px 6px; | padding:3px 6px 3px 6px; | ||
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border-style:solid;">Phase II</span> | border-style:solid;">Phase II</span> | ||
+ | |- | ||
+ | |} | ||
*[[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 [[Mitotane (Lysodren)]] dose is increased as tolerated up to 4000 mg/day or maximum tolerated dose | *[[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 [[Mitotane (Lysodren)]] dose is increased as tolerated up to 4000 mg/day or maximum tolerated dose | ||
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*[[Cisplatin (Platinol)]] 40 mg/m2 IV once per day on days 2 & 9 | *[[Cisplatin (Platinol)]] 40 mg/m2 IV once per day on days 2 & 9 | ||
− | '''28-day | + | '''28-day cycle x up to 6 cycles, given until progression of disease, unacceptable toxicity, or patient refusal''' |
===References=== | ===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''' [http://www.ncbi.nlm.nih.gov/pubmed/16172198 PubMed] | # 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''' [http://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 | + | # 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''' [http://www.ncbi.nlm.nih.gov/pubmed/22551107 PubMed] |
==Mitotane & Streptozocin {{#subobject:bd8397|Regimen=1}}== | ==Mitotane & Streptozocin {{#subobject:bd8397|Regimen=1}}== |
Revision as of 00:04, 4 October 2015
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14 regimens on this page
20 variants on this page
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Adrenal gland tumors, adrenocortical carcinoma - adjuvant therapy
Mitotane (Lysodren)
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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, Wängberg et al. 2010
Level of Evidence: Phase II
Patients started on adjuvant mitotane within 4 weeks of their surgical resection.
- 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, Mitotane (Lysodren) dose was adjusted to achieve a target therapeutic drug level of 14 to 20 mg/L
2 to 3-year course
Regimen #2, Haak et al. 1994
Level of Evidence: 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."
- 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
2-year course "if resection was judged to be complete or for 1 year after apparent disappearance of the tumour"
Supportive medications:
- Hydrocortisone (Cortef) 30 to 120 mg per day or Fludrocortisone (Florinef) 0.1 to 0.4 mg per day
- Metoclopramide (Reglan) and Loperamide (Imodium) prn "gastrointestinal side-effects"
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. link to original article 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. link to original article contains verified protocol PubMed content property of 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. link to original article 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. doi: 10.1200/JCO.2008.17.2775. Epub 2009 Aug 10. link to original article 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. doi: 10.1677/ERC-09-0190. Print 2010 Mar. link to original article contains verified protocol PubMed
Mitotane & Streptozocin
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Regimen, Khan et al. 2010
Level of Evidence: 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
21-day cycles; duration of therapy not clearly specified
Supportive medications:
- 5-HT3 antagonists prior to streptozocin
- Hydrocortisone (Cortef) 25 to 100 mg/day
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. link to original article contains verified protocol PubMed
Adrenal gland tumors, adrenocortical carcinoma - recurrent, locally advanced, or metastatic disease
Mitotane (Lysodren)
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Regimen, Veytsman et al. 2009
- Mitotane (Lysodren) 1000 to 2000 mg PO per day (frequency not specified, such as whether the total daily dose was divided into a few doses throughout the day); then increase daily dose of Mitotane (Lysodren) by 1000 to 2000 mg every 1 to 2 weeks to the maximum tolerated dose, not to exceed 6000 mg ("never > 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. doi: 10.1200/JCO.2008.17.2775. Epub 2009 Aug 10. link to original article contains verified protocol PubMed
Mitotane & EDP
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EDP: Etoposide, Doxorubicin, Platinol (Cisplatin)
Regimen #1
Study | Evidence | Comparator |
Fassnacht et al. 2012 (FIRM-ACT) | Phase III | Mitotane & Streptozocin |
Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.
- 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/m2 IV once per day on days 2 to 4
- Doxorubicin (Adriamycin) 40 mg/m2 IV once on day 1
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 3 & 4
Supportive medications:
- Glucocorticoid replacement was recommended in all patients except those with persistent Cushing's syndrome.
28-day cycles
Regimen #2
Study | Evidence |
Berruti et al. 2005 | Phase II |
- 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 Mitotane (Lysodren) dose is increased as tolerated up to 4000 mg/day or maximum tolerated dose
- Etoposide (Vepesid) 100 mg/m2 IV once per day on days 5 to 7
- Doxorubicin (Adriamycin) 20 mg/m2 IV once per day on days 1 & 8
- Cisplatin (Platinol) 40 mg/m2 IV once per day on days 2 & 9
28-day cycle x 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. link to original article contains verified protocol 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. link to original article contains verified protocol PubMed
Mitotane & Streptozocin
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Regimen, Fassnacht et al. 2012 (FIRM-ACT)
Level of Evidence: Phase III
Mitotane is started at least 1 week before the other chemotherapy; the rest of the therapy is as described below.
- Mitotane (Lysodren) on days 1 to 21, with target mitotane trough of 14 to 20 mg/L (initial dose and frequency not specified)
- Streptozocin (Zanosar) 1000 mg IV once per day on days 1 to 5 of cycle 1; then Streptozocin (Zanosar) 2000 mg IV once on day 1 of cycles 2 and on
21-day cycles
Supportive medications:
- "Glucocorticoid replacement was recommended in all patients except those with persistent Cushing's syndrome."
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. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2. link to original article contains verified protocol PubMed
Carcinoid tumors
Interferon alfa-2b (Intron-A)
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Regimen, Faiss et al. 2003
Level of Evidence: Phase III
- Interferon alfa-2b (Intron-A) 5 million units SC given once per day, 3 times per week
given until progression of disease; patients in Faiss et al. 2003 who progressed on monotherapy then received combination lanreotide & interferon alfa
References
- Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed
Lanreotide (Somatuline)
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Regimen, Faiss et al. 2003
Level of Evidence: Phase III
- Lanreotide (Somatuline) 1 mg SC TID
given until progression of disease; patients in Faiss et al. 2003 who progressed on monotherapy then received combination lanreotide & interferon alfa
References
- Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed
Lanreotide & Interferon alfa-2b
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Regimen, Faiss et al. 2003
Level of Evidence: Phase III
- Lanreotide (Somatuline) 1 mg SC TID
- Interferon alfa-2b (Intron-A) 5 million units SC given once per day, 3 times per week
References
- Faiss S, Pape UF, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B; International Lanreotide and Interferon Alfa Study Group. Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors--the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol. 2003 Jul 15;21(14):2689-96. link to original article contains verified protocol PubMed
Octreotide (Sandostatin)
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Regimen #1, Oberg et al. 2004
Octreotide immediate release (IR)
- 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" Octreotide (Sandostatin) 0.15 mg SC TID
patients may transition to octreotide long-acting release (LAR) treatment as described below; treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms
Octreotide long-acting release (LAR)
- 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 200–600 µg/day [0.2 to 0.6 mg/day], LAR 20 mg should be tried, and if total IR dose is 750–1500 µg/day [0.75 to 1.5 mg/day], LAR 30 mg should be tried."
- Octreotide (Sandostatin) (dose not specified) SC as needed for additional symptom control
28-day cycles; treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms
Regimen #2, Rinke et al. 2009 (PROMID)
Level of Evidence: Phase III
- 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
Regimen #3, Kvols et al. 1986
Level of Evidence: Phase II
- Octreotide (Sandostatin) 0.15 mg SC BID on days 1 & 2, then Octreotide (Sandostatin) 0.15 mg TID on days 3 and on
"treatment was continued for as long as a clinical improvement was maintained"
Regimen #4, Kölby et al. 2003
Level of Evidence: Randomized Phase II, >20 per arm
- Octreotide (Sandostatin) 0.1 mg SC BID; patients with persistent carcinoid symptoms could receive increased doses up to Octreotide (Sandostatin) 0.2 mg SC TID
References
- Kvols LK, Moertel CG, O'Connell MJ, Schutt AJ, Rubin J, Hahn RG. Treatment of the malignant carcinoid syndrome. Evaluation of a long-acting somatostatin analogue. N Engl J Med. 1986 Sep 11;315(11):663-6. link to original article contains verified protocol PubMed
- 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
- 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
- Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. link to original article contains verified protocol PubMed
- Review: Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. link to original article contains verified protocol PubMed
- 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. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24. link to original article contains verified protocol PubMed
- Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011 Dec 10;378(9808):2005-12. doi: 10.1016/S0140-6736(11)61742-X. Epub 2011 Nov 25. link to original article contains verified protocol PubMed
Octreotide & Everolimus
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Regimen #1, Pavel et al. 2011 (RADIANT-2)
Level of Evidence: Phase III
- Octreotide LAR (Sandostatin LAR) 30 mg IM once every 28 days
- Everolimus (Afinitor) 10 mg PO once per day
given until progression of disease or unacceptable toxicity
Regimen #2, Yao et al. 2008
Level of Evidence: Phase II
- 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
- 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."
28-day cycles x 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. doi: 10.1200/JCO.2008.16.7858. link to original article contains verified protocol PubMed
- Pavel ME, Hainsworth JD, Baudin E, Peeters M, Hörsch D, Winkler RE, Klimovsky J, Lebwohl D, Jehl V, Wolin EM, Oberg K, Van Cutsem E, Yao JC; RADIANT-2 Study Group. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011 Dec 10;378(9808):2005-12. doi: 10.1016/S0140-6736(11)61742-X. Epub 2011 Nov 25. link to original article contains verified protocol PubMed
Octreotide & Interferon alfa
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Regimen, Kölby et al. 2003
Level of Evidence: Randomized Phase II, >20 per arm
Kölby et al. 2003 did not specifically say whether Interferon alfa-2b (Intron-A) or Interferon alfa-2a (Roferon-A) was used.
- Octreotide (Sandostatin) 0.1 mg SC BID; patients with persistent carcinoid symptoms could receive increased doses up to Octreotide (Sandostatin) 0.2 mg SC TID
- Interferon alfa-2b (Intron-A) 3 million units (route not specified) given once per day, 3 days per week; increased as needed based on symptoms up to Interferon alfa-2b (Intron-A) 5 million units (route not specified) given once per day, 5 days 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
- Kölby L, Persson G, Franzén S, Ahrén B. Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg. 2003 Jun;90(6):687-93. link to original article contains verified protocol PubMed
Placebo
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Regimen
Level of Evidence: Phase III
No 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. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24. link to original article contains verified protocol PubMed
Temozolomide (Temodar)
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Regimen
Level of Evidence: Phase II
- Temozolomide (Temodar) 100 or 150 mg/m2 PO once per day on days 1 to 5; then Temozolomide (Temodar) dose may be increased in the following cycle(s) as tolerated up to 200 mg/m2 PO once per day on days 1 to 5
28-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications:
- Tropisetron (Navoban) (dose/route/schedule not specified) routinely used as an antiemetic
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. link to original article contains verified protocol PubMed
Neuroendocrine tumors of unknown primary, poorly differentiated (high-grade) neuroendocrine tumors
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 (Afinitor)
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Regimen, Yao et al. 2010 & Yao et al. 2011 (RADIANT-3)
Level of Evidence: Phase III
- 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. doi: 10.1200/JCO.2009.24.2669. Epub 2009 Nov 23. link to original article contains verified protocol 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. doi: 10.1056/NEJMoa1009290. link to original article contains verified protocol PubMed
- 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. doi: 10.1158/0008-5472.CAN-12-3923. Epub 2013 Feb 22. link to original article PubMed
Lanreotide (Somatuline) Depot/Autogel
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Regimen, Caplin et al. 2014 (CLARINET) & NET729
Level of Evidence: Phase III
- Lanreotide (Somatuline) Depot/Autogel 120 mg deep subcutaneous injection once on day 1
4-week cycles x 96 weeks (CLARINET), until progression of disease, or unacceptable toxicity; patients in NET729 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. link to original article contains verified protocol PubMed
- Lanreotide (Somatuline) package insert
- NIHR (National Institute for Health Research) Horizon Scanning Centre, School of Health & Population Sciences, University of Birmingham. Lanreotide for unresectable, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours – first line
- ClinicalTrials.gov: Study of Lanreotide Autogel 120mg in Patients With Non-functioning Entero- Pancreatic Endocrine Tumour (NET729)
Lanreotide & Interferon alfa
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Regimen, Fjällskog et al. 2002
Level of Evidence: Pilot, <20 patients reported
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.
- 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. link to original article PubMed
Octreotide (Sandostatin)
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Regimen #1, Oberg et al. 2004
Octreotide immediate release (IR)
- 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" Octreotide (Sandostatin) 0.15 mg SC TID
patients may transition to octreotide long-acting release (LAR) treatment as described below; treatment continued indefinitely unless patients have unmanageable side-effects or insufficient control of symptoms
Octreotide long-acting release (LAR)
- 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 200–600 µg/day, LAR 20 mg should be tried, and if total IR dose is 750–1500 µg/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, Rinke et al. 2009 (PROMID)
Level of Evidence: Phase III
- 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
- 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
- Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, Wiedenmann B. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol. 2004 Jun;15(6):966-73. link to original article contains verified protocol PubMed
- 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. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24. link to original article contains verified protocol PubMed
Octreotide & Everolimus
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Regimen #1, Yao et al. 2010
Level of Evidence: 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.
- 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, Yao et al. 2008
Level of Evidence: Phase II
- 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
- 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."
28-day cycles x 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. doi: 10.1200/JCO.2008.16.7858. link to original article contains verified protocol 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. doi: 10.1200/JCO.2009.24.2669. Epub 2009 Nov 23. link to original article contains verified protocol PubMed
Octreotide & Interferon alfa
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Regimen, Fjällskog et al. 2002
Level of Evidence: Pilot, <20 patients reported
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.
- 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. 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
- 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. link to original article PubMed
Placebo
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Regimen
Level of Evidence: Phase III
No 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. doi: 10.1200/JCO.2009.22.8510. Epub 2009 Aug 24. link to original article contains verified protocol 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. doi: 10.1056/NEJMoa1003825. link to original article contains verified protocol 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. doi: 10.1056/NEJMoa1009290. link to original article contains verified protocol PubMed
Streptozocin & Doxorubicin
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Regimen
Level of Evidence: Phase III
- Streptozocin (Zanosar) 500 mg/m2 IV once per day on days 1 to 5
- Doxorubicin (Adriamycin) 50 mg/m2 IV once per day on days 1 & 22
6-week 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. link to original article contains verified protocol PubMed
Streptozocin, Doxorubicin, Fluorouracil (FAS)
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FAS: Fluorouracil, Adriamycin, Streptozocin
Regimen
Level of Evidence: Retrospective
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 to 5
- Streptozocin (Zanosar) 400 mg/m2 IV bolus once per day on days 1 to 5
- Doxorubicin (Adriamycin) 40 mg/m2 IV bolus once on day 1
28-day cycles, given until progression of disease, unacceptable toxicity, or patient intolerance
References
- 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 verified protocol PubMed
Streptozocin & Fluorouracil
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Regimen
Level of Evidence: Phase III
- 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
6-week 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. link to original article contains verified protocol PubMed
Sunitinib (Sutent)
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Regimen, Raymond et al. 2011
Level of Evidence: Phase III
- 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. doi: 10.1056/NEJMoa1003825. link to original article contains verified protocol PubMed
Temozolomide (Temodar)
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Regimen
Level of Evidence: Phase II
- Temozolomide (Temodar) 100 or 150 mg/m2 PO once per day on days 1 to 5; then Temozolomide (Temodar) dose may be increased in the following cycle(s) as tolerated up to 200 mg/m2 PO once per day on days 1 to 5
28-day cycles, given until progression of disease or unacceptable toxicity
Supportive medications:
- Tropisetron (Navoban) (dose/route/schedule not specified) routinely used as an antiemetic
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. link to original article contains verified protocol PubMed
Temozolomide & Bevacizumab
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Regimen
Level of Evidence: Phase II
- Temozolomide (Temodar) 150 mg/m2 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
28-day cycles, given until progression of disease or unacceptable toxicity
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
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. doi: 10.1200/JCO.2011.40.3147. Epub 2012 Jul 9. link to original article contains verified protocol PubMed
Temozolomide & Capecitabine
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Regimen, Strosberg et al. 2011
Level of Evidence: Retrospective
- Temozolomide (Temodar) 200 mg/m2 PO once per day at bedtime on days 10 to 14
- Capecitabine (Xeloda) 750 mg/m2 PO BID on days 1 to 14
28-day cycles
Supportive medications:
- Ondansetron (Zofran) 8 mg (route not specified) prior to each dose of temozolomide
References
- 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. doi: 10.1002/cncr.25425. Epub 2010 Sep 7. link to original article contains verified protocol PubMed
Temozolomide & Thalidomide
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Regimen, Kulke et al. 2006
Level of Evidence: Phase II
- Temozolomide (Temodar) 150 mg/m2 PO once per day on days 1 to 7, 15 to 21
- Thalidomide (Thalomid) 200 mg PO once per day on days 1 to 28
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. link to original article contains verified protocol PubMed
Pheochromocytoma
Cyclophosphamide, Vincristine, Dacarbazine (CVD)
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CVD: Cyclophosphamide, Vincristine, Dacarbazine
Regimen, Averbuch et al. 1988
Level of Evidence: Pilot, <20 patients reported
- Cyclophosphamide (Cytoxan) 750 mg/m2 IV once on day 1
- Vincristine (Oncovin) 1.4 mg/m2 IV once on day 1
- Dacarbazine (DTIC) 600 mg/m2 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. link to original article contains protocol PubMed
131I-Metaiodobenzylguanidine (131I-MIBG)
Also known as m-[131I]iodobenzylguanidine ([131I]MIBG).
Regimen #1, Rose et al. 2003
Level of Evidence: Pilot, <20 patients reported
Patients underwent stem cell harvest prior to treatment in case autologous stem cell infusion was needed.
- 131I-Metaiodobenzylguanidine (131I-MIBG) 12 to 18 mCi/kg (maximum single dose of 850 mCi) IV over 2 hours once on day 1
"Repeat 131I-MIBG treatments were administered on a case-by-case basis in an effort to improve the overall response"
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.
Regimen #2, Krempf et al. 1991
Level of Evidence: Pilot, <20 patients reported
- 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. link to original article contains protocol 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. link to original article contains verified protocol PubMed