Carcinoid syndrome medical therapy: Difference between revisions

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. NATIONAL CANCER INSTITUTE . http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq#link/_97_toc Accessed on September 22, 2015</ref>
. NATIONAL CANCER INSTITUTE . http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq#link/_97_toc Accessed on September 22, 2015</ref>
*[[Somatostatin]] analogs
*[[Somatostatin]] analogs
* Telotristat
*[[Interferons]]
*[[Interferons]]
*Treatment of hepatic metastases
*Treatment of hepatic metastases
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*Endocrine disturbances (e.g., [[hypothyroidism]], [[hypoglycemia]], or [[hyperglycemia]])
*Endocrine disturbances (e.g., [[hypothyroidism]], [[hypoglycemia]], or [[hyperglycemia]])
*Gastric atony
*Gastric atony
 
==Telotristat==
===Interferons===
===Interferons===



Revision as of 14:45, 26 December 2018

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

Overview

The predominant therapy for carcinoid syndrome is surgical resection. Supportive therapy for carcinoid syndrome includes somatostatin analogs, interferons, and radionuclides.

Medical Therapy

Standard treatments for patients with gastrointestinal (GI) carcinoid tumors include the following:[1]

Somatostatin Analogs

  • The development of long-acting and depot formulations of somatostatin analogs has been important in the amelioration of symptoms of carcinoid syndrome. The result has been a substantial improvement in quality of life with relatively mild adverse effects.
  • Experimentally, somatostatin has been shown to have a cytostatic effect on tumor cells. This effect involves hyperphosphorylation of the retinoblastoma gene product and G1 cell cycle arrest, in addition to somatostatin receptor (SSTR) subtype 3 [sst(3)]-mediated (and to a lesser extent, SSTR subtype [sst(2)]-mediated) apoptosis.
  • Somatostatin also appears to have some antiangiogenic properties. However, only a small number of patients treated with somatostatin analog therapy experience partial tumor regression.
  • Octreotide, a short-acting somatostatin analog and the first biotherapeutic agent used in the management of carcinoid tumors, exhibits beneficial effects that are limited to symptom relief, with about 70% of patients experiencing resolution of diarrhea or flushing.
  • Lanreotide, a long-acting somatostatin analog administered every 10 to 14 days, has an efficacy similar to that of octreotide and an agreeable formulation for patient use. The effects of lanreotide on symptom relief are comparable to those of octreotide, with 75% to 80% of patients reporting decreased diarrhea and flushing. However, there appears to be little improvement in tumor responses over shorter-acting octreotide.
  • Depot formulations include long-acting repeatable (LAR) octreotide and a slow-release depot preparation of lanreotide.
  • The typical duration of treatment with somatostatin analogs is approximately 12 months because of the development of tachyphylaxis (reported less frequently with long-acting formulations) and/or disease progression.

Adverse effects of somatostatin analog administration include:

Telotristat

Interferons

  • The most researched interferon in the treatment of carcinoid disease is interferon-alpha (IFN-alpha); comparable to somatostatin analogs, the most pronounced effects of IFN-alpha are inhibition of disease progression and symptom relief, with approximately 75% of patients reporting the resolution of diarrhea or flushing.
  • IFN-alpha may show greater anti-tumor activity than somatostatin analogs. Both single-agent and multiagent chemotherapeutics appear to have little role in the management of these essentially chemoresistant tumors, no protocol has shown objective tumor response rates greater than 15%.

Treatment of Hepatic Metastases

The management of hepatic metastases may include:

Radionuclides

The four radionuclide conjugates most commonly used in the treatment of carcinoid disease are:

  • 131I-MIBG (iodine-131-meta-iodobenzylguanidine)
  • Indium-111
  • Yttrium-90
  • Lutetium-177

Management of Carcinoid-Related Fibrosis

Currently, there is no effective pharmacologic therapy for bowel obstruction and heart failure secondary to peritoneal fibrosis and right-sided valvular fibrosis respectively. In the instance of bowel obstruction, surgical lysis of the adhesions often is technically demanding because of the cocoon-like effects of extensive fibrosis stimulated by the various tumor-derived growth factors. Valvular replacement usually is required to manage carcinoid heart disease.

Symptomatic Therapy

  • In addition to the use of long-acting depot formulations of somatostatin analogs as the principal agents in the amelioration of carcinoid symptoms, the nonspecific supportive care of patients includes, advising them to avoid factors that induce flushing or bronchospastic episodes including the following:
  • Diarrhea may be treated with conventional anti-diarrheal agents such as loperamide or diphenoxylate, more pronounced diarrhea may be treated with the 5-HT receptor subtype 2 antagonist cyproheptadine, which is effective in as many as 50% of patients and may also help alleviate anorexia or cachexia in patients with a malignant carcinoid syndrome.

References

  1. Treatment Option Overview for GI Carcinoid Tumors . NATIONAL CANCER INSTITUTE . http://www.cancer.gov/types/gi-carcinoid-tumors/hp/gi-carcinoid-treatment-pdq#link/_97_toc Accessed on September 22, 2015


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