Carcinoid syndrome medical therapy
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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
Symptomatic therapy Symptomatic relief may be provided by any of the following medical therapies:
- Octreotide (somatostatin analogue- neutralizes serotonin and decreases urinary 5-HIAA)
- Methysergide maleate (antiserotonin agent but not used because of serious side effect of retroperitoneal fibrosis)
- Cyproheptadine (antihistamine)
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%.