eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract

Carcinoid Tumor, Intestinal: Treatment & Medication

Author: Hemant Singhal, MD, MBBS, FRCSE, FRCS(C), Senior Lecturer, Department of Surgery, Imperial College School of Medicine, UK; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK
Coauthor(s): Kanchan Kaur, MBBS, MS, MRCS (Ed), Clinical Fellow, Department of Surgery, Northwick Park Hospital, UK; Alan A Saber, MD, MS, FACS, Chief, Minimally Invasive Surgery and Bariatric Surgery, Associate Professor, Department of Surgery, Michigan State University; Charles Zammit, MD, Senior Specialist Registrar, Department of Surgery, Breast Unit Charing Cross Hospital of London, England; Michael K McLeod, MD, FACE, FACS, Professor of Surgery and Program Director, Integrated General Surgery Program, Department of Surgery, Michigan State University College of Human Medicine
Contributor Information and Disclosures

Updated: Jan 8, 2009

Treatment

Medical Care

Medical care is usually only for symptomatic relief.

  • Chemotherapy 
    • Response rates are variable but rarely exceed 30%. Results are usually short-lived (ie, <1-y duration). 5-Fluorouracil and streptozocin (Zanosar)–based regimens are commonly used in patients with metastatic carcinoid tumors. The value of using newer agents (eg, taxanes, gemcitabine [Gemzar], irinotecan [Camptosar]) remains unproven.
    • Chemotherapeutic regimens are only for palliative purposes; if eligible, patients should be put on a clinical trial of investigational therapy.
  • Radiation: This has only a palliative role, particularly for painful bony metastasis.
  • Other modalities  
    • High doses of sodium iodine-131–labeled metaiodobenzylguanidine, low-dose interferon alfa, and octreotide have all been used, with some reduction in symptoms; however, tumor reduction is rarely observed. When reductions occur, they are only transient.10 The somatostatin analog octreotide may provide control of carcinoid symptoms if findings on OctreoScan are positive or if somatostatin receptors are found in tumor tissue.
    • Patients with problematic diarrhea usually find benefit from antidiarrheal medication. Cyproheptadine and histamine-2 receptor blockers may be of benefit because they suppress the production of vasoactive amines or block their peripheral effects.

Surgical Care

Surgical resection is the standard therapeutic modality.

  • Appendiceal carcinoids  
    • For tumors smaller than 1.5 cm in greatest diameter that are confined to mucosa, appendicectomy is adequate, with no need for follow-up care. Cure rates are 100%.
    • Tumors 2 cm or larger in diameter, those at the base of the appendix, or those with mesenteric lymphadenopathy are not common but are considered potentially malignant. Consider more aggressive surgery in the form of a right hemicolectomy and lymphadenectomy, similar to that performed for colonic adenocarcinoma.
    • Invasion of only the mesoappendix does not alter the long-term prognosis, but cecal involvement necessitates further surgery.
  • Small bowel carcinoids  
    • At laparotomy, perform a thorough examination of the small bowel because multiple lesions are fairly common.
    • Macroscopic tumor size is a fairly good indictor of malignant potential. For tumors smaller than 1 cm in diameter, local resection is usually adequate. Tumors larger than 1.5 cm have a risk of recurrence, hence the need for a segmental bowel resection with lymphadenectomy.
  • Rectal carcinoids  
    • Tumor size is of essence with regard to the extent of resection.
    • Tumors of up to 1 cm in diameter require only local excision or fulguration, with cure rates close to 100%.11 Consider large tumors (>2 cm) malignant, and manage them similarly to adenocarcinoma of the rectum, with extensive resection. Tumors of 1-2 cm can be treated either by limited or more aggressive resection, with each case is guided according to the size, invasive nature, and anatomic location.
    • All patients except for those with lesions smaller than 1 cm require conscientious follow-up care.
  • Metastatic intestinal carcinoid - Possible options  
    • Surgery is considered worthwhile in most cases because this is the best form of palliation, regardless of whether the tumor is of the secretory type. Tailor the procedure accordingly, and avoid attempts at major debulking procedures.
    • All patients with advanced-stage carcinoid tumors should be evaluated for possible multimodal surgical therapy. Primary tumors should be resected, even in the presence of distant metastases to prevent future intestinal obstruction. The "wait and see" method of management of this slow-growing cancer no longer has merit.
    • Obstructive small bowel lesions could be resected (if possible) or bypassed.
    • Multiple liver metastases in patients with carcinoid syndrome are resected, cauterized, or ablated with percutaneous alcohol injections because this usually results in a dramatic relief of symptoms.
    • Hepatic artery ligation or embolization (eg, collagen fibers, gel foam, alcohol) can result in significant tumor necrosis and is of value in patients with bulky, inoperable, or symptomatic liver metastasis, with up to a 60% reduction of tumor bulk in some cases. This form of treatment can be combined with intrahepatic chemotherapeutic infusion. However, it can result in toxic effects, particularly fever, nausea, vomiting, and abdominal pain. Occasionally, the carcinoid symptoms may worsen.12

See related CME at An Aggressive Surgical Approach Leads to Long-term Survival in Patients With Pancreatic Endocrine Tumors. 

Medication

The goals of pharmacotherapy are to induce remission, reduce morbidity and prevent complications.

Antineoplastic agents

These agents inhibit cell growth and differentiation.


Streptozocin (Zanosar)

Cell-cycle phase-nonspecific antineoplastic agent that alkylates DNA, causing interstrand cross-linking. Also inhibits DNA synthesis by blocking incorporation of DNA precursor and inhibiting cell proliferation. May be helpful in symptom palliation for patients with progressive disease. Dosage is related to body surface area. May cause a complete remission of disease. Administration must be suspended only when desired response or toxicity occurs. Streptozocin may determine severe nephrotoxic effects.

Adult

500 mg/m2 IV for 5 consecutive d q4-6wk

Pediatric

Administer as in adults

Aminoglycosides, loop diuretics and doxorubicin may increase nephrotoxicity; phenytoin may decrease effects

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Severe nausea and vomiting is common; liver dysfunction can occur; renal toxicity is dose-related and cumulative; closely monitor renal, hepatic, and hematologic function

Antisecretory agents

These agents may provide control of carcinoid symptoms.


Octreotide (Sandostatin)

Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has multitude of other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.

Adult

50 mcg SC tid initially; may increase dose to 500 mcg tid
Doses of 300-600 mcg/d or higher seldom result in additional biochemical benefit

Pediatric

1-10 mcg/kg/d IV/SC; not to exceed 1500 mcg/d

May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers and calcium channel blockers may need dosage adjustments

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adverse effects primarily related to altered GI motility, and include nausea, abdominal pain, diarrhea and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones, (insulin, glucagon and GH) hypo- or hyperglycemia may be seen; bradycardia, cardiac conduction abnormalities and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism may also occur; exercise caution in patients with renal impairment; cholelithiasis may occur

More on Carcinoid Tumor, Intestinal

Overview: Carcinoid Tumor, Intestinal
Differential Diagnoses & Workup: Carcinoid Tumor, Intestinal
Treatment & Medication: Carcinoid Tumor, Intestinal
Follow-up: Carcinoid Tumor, Intestinal
Multimedia: Carcinoid Tumor, Intestinal
References
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References

  1. Oberndorfer S. Karzinoide tumoren des du¨nndarms. Frankfurt Zietschrift fur Pathologie. 1907;1:426–429.

  2. Marshall JB, Bodnarchuk G. Carcinoid tumors of the gut. Our experience over three decades and review of the literature. J Clin Gastroenterol. Mar 1993;16(2):123-9. [Medline].

  3. Thorson A, Biorck G, Bjorkman G, Waldenstrom J. Malignant carcinoid of the small intestine with metastases to the liver, valvular disease of the right side of the heart (pulmonary stenosis and tricuspid regurgitation without septal defects), peripheral vasomotor symptoms, bronchoconstriction, and an unusual type of cyanosis; a clinical and pathologic syndrome. Am Heart J. Jun 1954;47(5):795-817. [Medline].

  4. Pearse AG. The cytochemistry and ultrastructure of polypeptide hormone-producing cells of the APUD series and the embryologic, physiologic and pathologic implications of the concept. J Histochem Cytochem. May 1969;17(5):303-13. [Medline].

  5. American Cancer Society. Statistics for 2008. [Full Text].

  6. Surveillance, Epidemiology, and End Results (SEER) Program. Public-Use Data (1973-1998), National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch, released April 2001, based on the November 2000 submission. Available at http://seer.cancer.gov/.

  7. Deans GT, Spence RA. Neoplastic lesions of the appendix. Br J Surg. Mar 1995;82(3):299-306. [Medline].

  8. Sugimoto E, Lorelius LE, Eriksson B, Oberg K. Midgut carcinoid tumours. CT appearance. Acta Radiol. Jul 1995;36(4):367-71. [Medline].

  9. Ruszniewski P, Amouyal P, Amouyal G, Grange JD, Mignon M, Bouche O, et al. Localization of gastrinomas by endoscopic ultrasonography in patients with Zollinger-Ellison syndrome. Surgery. Jun 1995;117(6):629-35. [Medline].

  10. Diaco DS, Hajarizadeh H, Mueller CR, Fletcher WS, Pommier RF, Woltering EA. Treatment of metastatic carcinoid tumors using multimodality therapy of octreotide acetate, intra-arterial chemotherapy, and hepatic arterial chemoembolization. Am J Surg. May 1995;169(5):523-8. [Medline].

  11. Mani S, Modlin IM, Ballantyne G, Ahlman H, West B. Carcinoids of the rectum. J Am Coll Surg. Aug 1994;179(2):231-48. [Medline].

  12. Carrasco CH, Charnsangavej C, Ajani J, Samaan NA, Richli W, Wallace S. The carcinoid syndrome: palliation by hepatic artery embolization. AJR Am J Roentgenol. Jul 1986;147(1):149-54. [Medline].

  13. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

  14. Ahlman H, Wangberg B, Jansson S, Friman S, Olausson M, Tylen U, et al. Interventional treatment of gastrointestinal neuroendocrine tumours. Digestion. 2000;62 Suppl 1:59-68. [Medline].

  15. Anthony L, Johnson D, Hande K, Shaff M, Winn S, Krozely M, et al. Somatostatin analogue phase I trials in neuroendocrine neoplasms. Acta Oncol. 1993;32(2):217-23. [Medline].

  16. Boudreaux JP, Putty B, Frey DJ, Woltering E, Anthony L, Daly I, et al. Surgical treatment of advanced-stage carcinoid tumors: lessons learned. Ann Surg. Jun 2005;241(6):839-45; discussion 845-6. [Medline].

  17. Chen F, O'Dorisio MS, Hermann G, Hayes J, Malarkey WB, O'Dorisio TM. Mechanisms of action of long-acting analogs of somatostatin. Regul Pept. Apr 8 1993;44(3):285-95. [Medline].

  18. Eriksson B, Orlefors H, Sundin A, Skogseid B, Langstrom B, Bergstrom M, et al. Positron emission tomography in neuroendocrine tumours. Ital J Gastroenterol Hepatol. Oct 1999;31 Suppl 2:S167-71. [Medline].

  19. Godwin JD 2nd. Carcinoid tumors. An analysis of 2,837 cases. Cancer. Aug 1975;36(2):560-9. [Medline].

  20. Gorden P, Comi RJ, Maton PN, Go VL. NIH conference. Somatostatin and somatostatin analogue (SMS 201-995) in treatment of hormone-secreting tumors of the pituitary and gastrointestinal tract and non-neoplastic diseases of the gut. Ann Intern Med. Jan 1 1989;110(1):35-50. [Medline].

  21. Hajarizadeh H, Ivancev K, Mueller CR, Fletcher WS, Woltering EA. Effective palliative treatment of metastatic carcinoid tumors with intra-arterial chemotherapy/chemoembolization combined with octreotide acetate. Am J Surg. May 1992;163(5):479-83. [Medline].

  22. Hofland LJ, van Hagen PM, Lamberts SW. Functional role of somatostatin receptors in neuroendocrine and immune cells. Ann Med. Oct 1999;31 Suppl 2:23-7. [Medline].

  23. Hou W, Schubert ML. Treatment of gastric carcinoids. Curr Treat Options Gastroenterol. Mar 2007;10(2):123-33. [Medline].

  24. Krenning EP, de Jong M, Kooij PP, Breeman WA, Bakker WH, de Herder WW, et al. Radiolabelled somatostatin analogue(s) for peptide receptor scintigraphy and radionuclide therapy. Ann Oncol. 1999;10 Suppl 2:S23-9. [Medline].

  25. Kulke MH, Mayer RJ. Carcinoid tumors. N Engl J Med. Mar 18 1999;340(11):858-68. [Medline].

  26. Neuroendocrine Carcinoma. In: Kantarjian H, Wolff R, Koller C, eds. M D Anderson Manual of Medical Oncology. New York: McGraw-Hill; 2006:449-459.

  27. Maroun J, Kocha W, Kvols L, Bjarnason G, Chen E, Germond C, et al. Guidelines for the diagnosis and management of carcinoid tumours. Part 1: The gastrointestinal tract. A statement from a Canadian National Carcinoid Expert Group. Curr Oncol. Apr 2006;13(2):67-76. [Medline].

  28. McCarthy KE, Woltering EA, Espenan GD, Cronin M, Maloney TJ, Anthony LB. In situ radiotherapy with 111In-pentetreotide: initial observations and future directions. Cancer J Sci Am. Mar-Apr 1998;4(2):94-102. [Medline].

  29. Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. Feb 15 2003;97(4):934-59. [Medline].

  30. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer. Feb 15 1997;79(4):813-29. [Medline].

  31. Moertel CG, Johnson CM, McKusick MA, Martin JK Jr, Nagorney DM, Kvols LK, et al. The management of patients with advanced carcinoid tumors and islet cell carcinomas. Ann Intern Med. Feb 15 1994;120(4):302-9. [Medline].

  32. Moertel CG, Kvols LK, O'Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer. Jul 15 1991;68(2):227-32. [Medline].

  33. Oberg K. Established clinical use of octreotide and lanreotide in oncology. Chemotherapy. 2001;47 Suppl 2:40-53. [Medline].

  34. Oberg K. Interferon in the management of neuroendocrine GEP-tumors: a review. Digestion. 2000;62 Suppl 1:92-7. [Medline].

  35. Oberg K, Stridsberg M. Chromogranins as diagnostic and prognostic markers in neuroendocrine tumours. Adv Exp Med Biol. 2000;482:329-37. [Medline].

  36. Perry RR, Vinik AI. Endocrine tumors of the gastrointestinal tract. Annu Rev Med. 1996;47:57-68. [Medline].

  37. Rubin J, Ajani J, Schirmer W, Venook AP, Bukowski R, Pommier R, et al. Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome. J Clin Oncol. Feb 1999;17(2):600-6. [Medline].

  38. Szilvas A, Szekely G, Szilvasi I, Sagi S, Jakab F. The importance of follow-up examinations in patients with carcinoid tumor. Hepatogastroenterology. Sep-Oct 2003;50(53):1452-3. [Medline].

  39. Vikman S, Essand M, Cunningham JL, de la Torre M, Oberg K, Totterman TH, et al. Gene expression in midgut carcinoid tumors: potential targets for immunotherapy. Acta Oncol. 2005;44(1):32-40. [Medline].

  40. Öberg K. Carcinoid Tumors: Current Concepts in Diagnosis and Treatment. Oncologist. 1998;3(5):339-345. [Medline].

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Further Reading

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Keywords

intestinal carcinoid tumor, intestinal carcinoid tumour, gastroenteropancreatic neoplasm, GEP, GEP neoplasm, well-differentiated gastrointestinal neuroendocrine cancer, GI neuroendocrine tumor, neuroendocrine tumor, neuroendocrine tumour, argentaffinoma, carcinoid syndrome, small bowel malignancy, irritable bowel syndrome, IBS, idiopathic flushing, intestinal tumor, intestinal tumour, GI tumor, GI tumour, gastrointestinal tumor, gastrointestinal tumour, intestinal malignancy, appendectomy, cancer of the appendix, carcinoid tumor of the appendix, carcinoid tumor of the small intestine, distal small bowel malignancy

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Contributor Information and Disclosures

Author

Hemant Singhal, MD, MBBS, FRCSE, FRCS(C), Senior Lecturer, Department of Surgery, Imperial College School of Medicine, UK; Consultant Surgeon, Northwick Park and St Marks Hospitals, UK
Hemant Singhal, MD, MBBS, FRCSE, FRCS(C) is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada and Royal College of Surgeons of Edinburgh
Disclosure: Nothing to disclose.

Coauthor(s)

Kanchan Kaur, MBBS, MS, MRCS (Ed), Clinical Fellow, Department of Surgery, Northwick Park Hospital, UK
Disclosure: Nothing to disclose.

Alan A Saber, MD, MS, FACS, Chief, Minimally Invasive Surgery and Bariatric Surgery, Associate Professor, Department of Surgery, Michigan State University
Alan A Saber, MD, MS, FACS is a member of the following medical societies: American College of Surgeons, American Society for Gastrointestinal Endoscopy, and American Society for Metabolic and Bariatric Surgery
Disclosure: Nothing to disclose.

Charles Zammit, MD, Senior Specialist Registrar, Department of Surgery, Breast Unit Charing Cross Hospital of London, England
Disclosure: Nothing to disclose.

Michael K McLeod, MD, FACE, FACS, Professor of Surgery and Program Director, Integrated General Surgery Program, Department of Surgery, Michigan State University College of Human Medicine
Michael K McLeod, MD, FACE, FACS is a member of the following medical societies: American Association of Clinical Endocrinologists, American Association of Endocrine Surgeons, American College of Surgeons, American Medical Association, Association for Academic Surgery, Central Surgical Association, International Association of Endocrine Surgeons, Michigan State Medical Society, Midwest Surgical Association, National Medical Association, Society of American Gastrointestinal and Endoscopic Surgeons, and Western Surgical Association
Disclosure: Nothing to disclose.

Medical Editor

Lodovico Balducci, MD, Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Benjamin Movsas, MD, Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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