Carcinoid syndrome medical therapy

Jump to navigation Jump to search

Carcinoid syndrome Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Carcinoid Syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Staging

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Carcinoid syndrome medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Carcinoid syndrome medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Carcinoid syndrome medical therapy

CDC on Carcinoid syndrome medical therapy

Carcinoid syndrome medical therapy in the news

Blogs on Carcinoid syndrome medical therapy

Directions to Hospitals Treating Carcinoid syndrome

Risk calculators and risk factors for Carcinoid syndrome medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Parminder Dhingra, M.D. [2] Anum Gull M.B.B.S.[3]

Overview

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

Medical Therapy

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

Somatostatin Analogs

  • Somatostatin analogs includes octreotide and lanreotide.
  • Somatostatin acts by binding to somatostatin receptors expressed on the majority of carcinoid tumors.
  • Flushing and diarrhea are significantly improved in over 80 percent of patients with the carcinoid syndrome with somatostatin therapy.[2]
  • 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.
  • 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.

Adverse effects of somatostatin analog administration include:

Telotristat

  • Telotristat is an oral inhibitor of tryptophan hydroxylase which catalyzes the conversion of l-tryptophan into serotonin..[3]
  • Tryptophan hydroxylase is an aromatic amino acid hydroxylase and is the rate-limiting enzyme in serotonin synthesis.
  • Somatostatin analogs (SSAs) are the mainstay of treatment, but are unable to ameliorate symptoms in all patients due to dose-limiting side effects and tachyphylaxis.
  • Telotristat represents a significant advance in the treatment of carcinoid syndrome diarrhea in patients who have inadequate control on long-acting SSAs and should be considered for patients with >4 bowel motions per day on SSAs

Interferons

  • The most researched interferon in the treatment of carcinoid disease is interferon-alpha (IFN-alpha).
  • Interferon-alpha (IFNα) is a cytokine that mediates anti-viral, anti-proliferative and anti-tumour activities.
  • Side-effects includes
  1. Flu-like symptoms
  2. Chronic fatigue
  3. Depression
  4. Anemia
  5. Neutropenia.

Treatment of Hepatic Metastases

The management of hepatic metastases may include:

Radionuclides

  • The use of somatostatin analogue radiolabeled peptide therapy (PRRT) provides radiation directed to the cells that express somatostatin receptors.[4]
  • 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
  • It is mandatory to quantify cells with somatostatin receptors using imaging prior to PRRT therapy.

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.[5]

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
  2. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA (September 2016). "EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL". Endocr Pract. 22 (9): 1068–80. doi:10.4158/EP151172.OR. PMID 27214300.
  3. Chan DL, Singh S (2018). "Developments in the treatment of carcinoid syndrome - impact of telotristat". Ther Clin Risk Manag. 14: 323–329. doi:10.2147/TCRM.S126143. PMC 5824756. PMID 29503551.
  4. Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Miederer M, Schreckenberger M, Krause BJ, Bengel FM, Bartenstein P, Biersack HJ, Pöpperl G, Baum RP (May 2016). "Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: A multi-institutional registry study with prospective follow-up". Eur. J. Cancer. 58: 41–51. doi:10.1016/j.ejca.2016.01.009. PMID 26943056.
  5. Modlin IM, Shapiro MD, Kidd M (December 2004). "Carcinoid tumors and fibrosis: an association with no explanation". Am. J. Gastroenterol. 99 (12): 2466–78. doi:10.1111/j.1572-0241.2004.40507.x. PMID 15571597.


Template:WikiDoc Sources