Insulinoma medical therapy: Difference between revisions

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__NOTOC__
__NOTOC__
{{CMG}} {{AE}}{{ADS}}
{{CMG}} {{AE}}{{ADS}}
{{Insulinoma}}
{{Insulinoma}}


==Overview==
==Overview==
Medical therapy is reserved for those who can't undergo the primary surgical therapy. Drugs commonly used for benign insulinoma are [[Diazoxide]], [[Octreotide]]/lanreotide, [[Phenytoin]], verapamil and everolimus. For malignant insulinoma, these drugs are used with the [[chemotherapy]] drugs [[Streptozocin]], 5 [[Fluorouracil]], [[Doxorubicin]][[Bevacizumab|, bevacizumab]] and [[Capecitabine]] in different combinations. For [[metastasis]] mainly going to [[liver]] regimens include [[hepatic artery]] [[embolization]], [[Radiation therapy|radiation]], chemo-embolization, [[ethanol]] ablation [[Radiofrequency ablation]] and [[Cryoablation]].
Medical therapy is reserved for those who are unable to undergo the primary surgical therapy. Drugs commonly used for benign insulinoma are [[diazoxide]], [[octreotide]]/lanreotide, [[phenytoin]], [[verapamil]] and [[everolimus]]. For malignant insulinoma, these drugs are used with the [[chemotherapy]] drugs [[streptozocin]], 5 [[fluorouracil]], [[doxorubicin]], [[bevacizumab]] and [[capecitabine]] in different combinations. For [[metastasis]] mainly going to [[liver]] regimens include [[hepatic artery]] [[embolization]], [[Radiation therapy|radiation]], chemo-embolization, [[ethanol]] ablation, [[radiofrequency ablation]], and [[cryoablation]].
 
==Medical Therapy==
==Medical Therapy==
*The primary treatment is surgical excision. Medical therapy is reserved for:
*The primary treatment is surgical excision. Medical therapy is reserved for:
**Those who can't undergo [[surgery]]
**Those who are unable to undergo [[surgery]]:
***High-risk patients
***High-risk patients
***Unresectable [[metastatic]] disease
***Unresectable [[metastatic]] disease
**Those who refuse to undergo [[surgery]]
**Those who refuse to undergo [[surgery]]:
* The medical therapy is mainly used to reduce/prevent symptoms of [[hypoglycemia]].
* The medical therapy is mainly used to reduce/prevent symptoms of [[hypoglycemia]].
*Pharmacologic medical therapies for insulinoma include [[diazoxide]], [[octreotide]]/[[lanreotide]], [[phenytoin]], [[verapamil]], and [[everolimus]].
*Pharmacologic medical therapies for insulinoma include [[diazoxide]], [[octreotide]]/[[lanreotide]], [[phenytoin]], [[verapamil]], and [[everolimus]].
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===1. '''Adult'''===
===1. '''Adult'''===
*'''Parenteral'''
*'''1.1 Parenteral'''
** Preferred regimen (1): [[Octreotide]] 30 mg IM (depot) every 4 weeks until tumor progression or death.
** Preferred regimen (1): [[Octreotide]] 30 mg IM (depot) every 4 weeks until [[tumor]] progression or death.
** Preferred regimen (2): [[Octreotide]] 100-500 μg SQ q 8-12h（can be increased to maximum 1500 μg daily）for 1 year.
** Preferred regimen (2): [[Octreotide]] 100-500 μg SQ q 8-12h（can be increased to maximum 1500 μg daily）for 1 year.
** Preferred regimen (3): [[Lanreotide]] 120 mg SQ every 4 weeks until tumor progression.
** Preferred regimen (3): [[Lanreotide]] 120 mg SQ every 4 weeks until [[tumor]] progression.
*'''Oral'''
*'''1.2 Oral'''
**Preferred regimen : [[Diazoxide]] 3-8 mg/kg OR 200-300 mg PO q8h for 14-21 days (1200 mg max to be divided in 3 doses and max is 400 mg/dose). <ref name="pmid3019020">{{cite journal |vauthors=Goode PN, Farndon JR, Anderson J, Johnston ID, Morte JA |title=Diazoxide in the management of patients with insulinoma |journal=World J Surg |volume=10 |issue=4 |pages=586–92 |year=1986 |pmid=3019020 |doi= |url=}}</ref><ref name="pmid9497974">{{cite journal |vauthors=Gill GV, Rauf O, MacFarlane IA |title=Diazoxide treatment for insulinoma: a national UK survey |journal=Postgrad Med J |volume=73 |issue=864 |pages=640–1 |year=1997 |pmid=9497974 |pmc=2431498 |doi= |url=}}</ref>
**Preferred regimen : [[Diazoxide]] 3-8 mg/kg OR 200-300 mg PO q8h for 14-21 days (1200 mg max to be divided in 3 doses and max is 400 mg/dose).<ref name="pmid3019020">{{cite journal |vauthors=Goode PN, Farndon JR, Anderson J, Johnston ID, Morte JA |title=Diazoxide in the management of patients with insulinoma |journal=World J Surg |volume=10 |issue=4 |pages=586–92 |year=1986 |pmid=3019020 |doi= |url=}}</ref><ref name="pmid9497974">{{cite journal |vauthors=Gill GV, Rauf O, MacFarlane IA |title=Diazoxide treatment for insulinoma: a national UK survey |journal=Postgrad Med J |volume=73 |issue=864 |pages=640–1 |year=1997 |pmid=9497974 |pmc=2431498 |doi= |url=}}</ref>
** Alternative regimen (1): [[Phenytoin]] 300-600 mg PO q daily. <ref name="MathurGorden2009">{{cite journal|last1=Mathur|first1=Aarti|last2=Gorden|first2=Philip|last3=Libutti|first3=Steven K.|title=Insulinoma|journal=Surgical Clinics of North America|volume=89|issue=5|year=2009|pages=1105–1121|issn=00396109|doi=10.1016/j.suc.2009.06.009}}</ref>
** Alternative regimen (1): [[Phenytoin]] 300-600 mg PO q daily. <ref name="MathurGorden2009">{{cite journal|last1=Mathur|first1=Aarti|last2=Gorden|first2=Philip|last3=Libutti|first3=Steven K.|title=Insulinoma|journal=Surgical Clinics of North America|volume=89|issue=5|year=2009|pages=1105–1121|issn=00396109|doi=10.1016/j.suc.2009.06.009}}</ref>
**Alternative regimen (2): [[Everolimus]] 10 mg PO q daily until disease progression.
**Alternative regimen (2): [[Everolimus]] 10 mg PO q daily until disease progression.
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===2. '''Pediatric'''===
===2. '''Pediatric'''===
2.1 [[Neonates]] and [[Infants]]:
* '''2.1 [[Neonates]] and [[Infants]]:'''
*'''Oral'''
**'''2.1.1 Oral'''
**Preferred regimen: [[Diazoxide]] initial dose: 10 mg/kg/day divided into 3 equal doses q 8 hours.
***Preferred regimen: [[Diazoxide]]
**Maintenance dosing range: 8 to 15 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours.<br>
****Initial dose: 10 mg/kg/day divided into 3 equal doses q 8 hours.
2.2 [[Children]] and [[Adolescent|adolescents]]- follow the adult regimen
****Maintenance dosing range: 8 to 15 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours.
 
* '''2.2 [[Children]] and [[Adolescent|adolescents]]'''
** Follow the adult regimen


==='''[[Malignant]] ([[metastatic]]) Insulinoma'''===
==='''[[Malignant]] ([[metastatic]]) Insulinoma'''===


'''[[Chemotherapy]]'''<br>It is used in the different combination of the following drugs:
'''1. [[Chemotherapy]]'''<br>It is used in the different combination of the following drugs:
* [[Streptozocin]] 500 mg/m<sup>2</sup>/day IV for 5 consecutive days every 6 weeks
* [[Streptozocin]] 500 mg/m<sup>2</sup>/day IV for 5 consecutive days every 6 weeks
* [[Doxorubicin]] 40-75 mg/m<sup>2</sup> IV every 21 to 28 days
* [[Doxorubicin]] 40-75 mg/m<sup>2</sup> IV every 21 to 28 days
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* [[Bevacizumab]]
* [[Bevacizumab]]
* [[Capecitabine]]
* [[Capecitabine]]
 
'''2. Liver-directed therapy''' (for [[metastasis]])
==='''Liver-directed therapy''' (for metastasis)===
*2.1 [[Radiation therapy|Radiation]]
*[[Radiation therapy|Radiation]]
**2.1.1 Selective internal radiation therapy
**Selective Internal Radiation Therapy
**2.1.2 Peptide receptor radionuclide therapy (PRRT): [[cytotoxic]] doses of [[radiation]] are given locally to the site of [[tumor]] (sometimes also called Radio-embolization)
**Peptide Receptor Radionuclide Therapy (PRRT) - [[cytotoxic]] doses of [[radiation]] are given locally to the site of tumor (also called Radio-embolization sometimes)
*2.2 [[Hepatic artery]] [[embolization]], chemo-embolization, and [[infusion]]. Infusion consists of:
*[[Hepatic artery]] [[embolization]], chemo-embolization, and [[infusion]]. Infusion consists of:
**2.2.1 [[Hepatic artery]] [[infusion]] (HIA): HIA is the administration of [[Chemotherapeutic agent|chemotherapeutic]] agents (high doses of [[streptozocin]] and [[5-FU]]) into the [[hepatic artery]]. Response rates are 0 to 100%.
**[[Hepatic artery]] [[infusion]] (HIA) - which is the administration of [[Chemotherapeutic agent|chemotherapeutic]] agents(high doses of [[streptozocin]] and [[5-FU]]) into the [[hepatic artery]]. Response rates are 0-100%.
**2.2.2 Isolated hepatic perfusion (IHP): HIP gave rise to minimally invasive, percutaneous hepatic perfusion.<ref name="MathurGorden2009">{{cite journal|last1=Mathur|first1=Aarti|last2=Gorden|first2=Philip|last3=Libutti|first3=Steven K.|title=Insulinoma|journal=Surgical Clinics of North America|volume=89|issue=5|year=2009|pages=1105–1121|issn=00396109|doi=10.1016/j.suc.2009.06.009}}</ref>
**Isolated hepatic perfusion (IHP) which gave rise to minimally invasive, percutaneous hepatic perfusion. <ref name="MathurGorden2009">{{cite journal|last1=Mathur|first1=Aarti|last2=Gorden|first2=Philip|last3=Libutti|first3=Steven K.|title=Insulinoma|journal=Surgical Clinics of North America|volume=89|issue=5|year=2009|pages=1105–1121|issn=00396109|doi=10.1016/j.suc.2009.06.009}}</ref>
*2.3 Percutaneous [[ethanol]] injection/ [[Ethanol]] ablation
*Percutaneous [[ethanol]] injection/ [[Ethanol]] ablation
*2.4 [[Radiofrequency ablation]] ([[RFA]])
*[[Radiofrequency ablation]] ([[RFA]])
*2.5 [[Cryoablation]]
*[[Cryoablation]]


==References==
==References==
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Latest revision as of 02:07, 27 November 2017

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]

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Overview

Medical therapy is reserved for those who are unable to undergo the primary surgical therapy. Drugs commonly used for benign insulinoma are diazoxide, octreotide/lanreotide, phenytoin, verapamil and everolimus. For malignant insulinoma, these drugs are used with the chemotherapy drugs streptozocin, 5 fluorouracil, doxorubicin, bevacizumab and capecitabine in different combinations. For metastasis mainly going to liver regimens include hepatic artery embolization, radiation, chemo-embolization, ethanol ablation, radiofrequency ablation, and cryoablation.

Medical Therapy

Benign Insulinoma

1. Adult

  • 1.1 Parenteral
    • Preferred regimen (1): Octreotide 30 mg IM (depot) every 4 weeks until tumor progression or death.
    • Preferred regimen (2): Octreotide 100-500 μg SQ q 8-12h（can be increased to maximum 1500 μg daily）for 1 year.
    • Preferred regimen (3): Lanreotide 120 mg SQ every 4 weeks until tumor progression.
  • 1.2 Oral
    • Preferred regimen : Diazoxide 3-8 mg/kg OR 200-300 mg PO q8h for 14-21 days (1200 mg max to be divided in 3 doses and max is 400 mg/dose).[1][2]
    • Alternative regimen (1): Phenytoin 300-600 mg PO q daily. [3]
    • Alternative regimen (2): Everolimus 10 mg PO q daily until disease progression.
    • Verapamil and Propranolol to control symptoms are used either as alone or in combination.
    • Glucocorticoids and glucagon have been used in combination with diazoxide.

2. Pediatric

  • 2.1 Neonates and Infants:
    • 2.1.1 Oral
      • Preferred regimen: Diazoxide
        • Initial dose: 10 mg/kg/day divided into 3 equal doses q 8 hours.
        • Maintenance dosing range: 8 to 15 mg/kg/day divided into 2 or 3 equal doses every 8 to 12 hours.

Malignant (metastatic) Insulinoma

1. Chemotherapy
It is used in the different combination of the following drugs:

2. Liver-directed therapy (for metastasis)

References

  1. ↑ Goode PN, Farndon JR, Anderson J, Johnston ID, Morte JA (1986). "Diazoxide in the management of patients with insulinoma". World J Surg. 10 (4): 586–92. PMID 3019020.
  2. ↑ Gill GV, Rauf O, MacFarlane IA (1997). "Diazoxide treatment for insulinoma: a national UK survey". Postgrad Med J. 73 (864): 640–1. PMC 2431498. PMID 9497974.
  3. ↑ 3.0 3.1 Mathur, Aarti; Gorden, Philip; Libutti, Steven K. (2009). "Insulinoma". Surgical Clinics of North America. 89 (5): 1105–1121. doi:10.1016/j.suc.2009.06.009. ISSN 0039-6109.


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