Carcinoid syndrome medical therapy: Difference between revisions
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===Symptomatic Therapy=== | ===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: | *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: | Advising them to avoid factors that induce flushing or bronchospastic episodes including the following: | ||
*Ingestion of alcohol, certain cheeses, capsaicin-containing foods, and nuts | :*Ingestion of alcohol, certain cheeses, capsaicin-containing foods, and nuts | ||
*Stressful situations | :*Stressful situations | ||
*Physical activity | :*Physical activity | ||
Diarrhea may be treated with conventional antidiarrheal 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. | *Diarrhea may be treated with conventional antidiarrheal 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. | ||
Histamine 1 receptor blockade with fexofenadine, loratadine, terfenadine, or diphenhydramine may be of benefit in treating skin rashes, particularly in histamine-secreting gastric carcinoid tumors. | *Histamine 1 receptor blockade with fexofenadine, loratadine, terfenadine, or diphenhydramine may be of benefit in treating skin rashes, particularly in histamine-secreting gastric carcinoid tumors. | ||
Bronchospasm can be managed with theophylline or beta-2 adrenergic receptor agonists such as albuterol. | *Bronchospasm can be managed with theophylline or beta-2 adrenergic receptor agonists such as albuterol. | ||
==References== | ==References== | ||
Revision as of 13:29, 22 September 2015
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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
For symptomatic relief of carcinoid sydromes medical therapy many include: octreotide, methysergide maleate, and cyproheptadine.
Medical Therapy
Standard treatments for patients with gastrointestinal (GI) carcinoid tumors include the following:
- Surgery
- Somatostatin analogs
- Interferons
- Treatment of hepatic metastases
- Radionuclides
- Management of carcinoid-related fibrosis
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.
In the treatment of carcinoids, 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:
- Nausea
- Cramping
- Loose stools
- Steatorrhea
- Cardiac conduction abnormalities and arrhythmias
- Endocrine disturbances (e.g., hypothyroidism, hypoglycemia, or, more commonly, hyperglycemia)
- Gastric atony
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 antitumor 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-
- Surgical resection
- Hepatic artery embolization
- Cryoablation and Radiofrequency ablation (RFA)
- Orthotopic liver transplantation
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
Bowel obstruction secondary to peritoneal fibrosis is the most common presenting symptom of small intestinal carcinoids. Heart failure secondary to right-sided valvular fibrosis represents a serious extraintestinal manifestation of carcinoid fibrosis and occurs in 20% to 70% of patients with metastatic disease; it accounts for as much as 50% of carcinoid mortality.Currently, there is no effective pharmacologic therapy for either clinical problem. 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:
- Ingestion of alcohol, certain cheeses, capsaicin-containing foods, and nuts
- Stressful situations
- Physical activity
- Diarrhea may be treated with conventional antidiarrheal 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.
- Histamine 1 receptor blockade with fexofenadine, loratadine, terfenadine, or diphenhydramine may be of benefit in treating skin rashes, particularly in histamine-secreting gastric carcinoid tumors.
- Bronchospasm can be managed with theophylline or beta-2 adrenergic receptor agonists such as albuterol.