eMedicine Specialties > Oncology > Carcinomas of the Gastrointestinal Tract
Malignant Carcinoid Syndrome: Treatment & Medication
Updated: Nov 19, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Systemic therapy should be used to control humorally mediated symptoms when the cancer spreads elsewhere. Initially, interferons and octreotide are useful in approximately 40% of patients.32 Histamine blockers may also be useful. Diarrhea generally responds to standard antidiarrheal medications, but serotonin antagonists should be administered, if necessary, to control diarrhea and malabsorption. Severe and prolonged carcinoid crises associated with bronchial or stomach carcinoids may respond to corticosteroid treatment. Therapy with MIBG has recently been considered but is only experimental; however, administering a radioactive somatostatin analogue (In-111 DTPA-D-Phe1 octreotide) is a form of internal radiation therapy, which is hopefully strong enough to kill the tumor cells.
- Somatostatin or its analogue may prevent flushing and other endocrine manifestations. Octreotide is a synthetic somatostatin analogue with high affinity for somatostatin receptors. Octreotide should be preferred to native somatostatin because of a longer half-life (average half-life of somatostatin is 2 min; that of octreotide is 2 h). Octreotide has demonstrated the ability to relieve symptoms in most patients, but tumor reduction is rarely observed.
- Patients benefit from specific drugs that either suppress production of vasoactive amines or block the peripheral effects. These agents include alpha-adrenergic blocking drugs, cyproheptadine, and H2-receptor blockers.
- Interferon-alpha may help control carcinoid symptoms or arrest tumor growth and reportedly may be effective in patients in whom octreotide treatment has failed; however, benefits are generally transient and accompanied by adverse effects.
- Radiotherapy or chemotherapy with streptozotocin, cisplatin, etoposide, and doxorubicin, either alone or in combination, has been used, and reports show some success; a good response occurs in only 20-30% of cases. The role of radiation therapy in the management of carcinoid tumors with distant metastasis is restricted to symptomatic palliation of the painful bone metastases. This therapy is not useful for treating liver metastases or for other nonskeletal tissues.
- Little evidence suggests that chemotherapy, either traditional or by continuous infusion, helps improve patient survival rates.
- Failure to respond to one chemotherapy combination does not necessarily mean another combination will also be ineffectual.
- The combination of interferon-alpha and continuous infusion of 5-fluorouracil (5-FU) has demonstrated antitumoral and antihormonal activity and can provide symptom palliation.
Surgical Care
Complete surgical removal of all tumor tissues, when feasible, is the best treatment because it may result in a complete and permanent cure. The aim of surgical therapy is to reduce the tumor mass and obtain symptom remission. Performing a curative resection, mass debulking, or hepatic embolization is possible.
Cytoreductive surgery has been reported to have the best impact on symptom regression and overall survival.33
- An extensive surgical excision, including the adjacent mesentery, must be performed.
- Surgery should always be considered in patients with large or extensive hepatic metastases involving surgically accessible areas of the liver.
- For lesions in the distal ileum, a right hemicolectomy is necessary to remove the lymphatic drainage adequately.
- For tumors located in the appendix that are smaller than 1.5 cm in diameter, appendectomy is suitable and curative in 100% of patients. The involvement of the mesoappendix does not alter the patient's prognosis, but invasion of the cecum mandates more radical surgery (eg, right hemicolectomy with regional lymphadenectomy). Carcinoids in children usually occur in the appendix, and the appendectomy results in a complete cure.
- Rectal carcinoids, if smaller than 1.5 cm in diameter, should be treated with local excision; if rectal carcinoids are larger than 1.5 cm, they must be considered malignant, and abdominoperineal resection (Miles operation) or low anterior resection should be performed.
- Hepatic transplantation has also been attempted in selected patients, with promising results; however, generalization for this treatment option, because it is extremely expensive and debilitating, is not possible without more long-term studies.
- Surgery should also be considered for resection of hepatic recurrence, even after previous resection, but only if the lesions are in an area where resection can be performed with minimal morbidity.
- The whole intestine should be examined at the time of surgery to detect eventual multiple lesions.34
- Chemoembolization with hepatic artery infusion of 5-FU or doxorubicin, combined with embolization of the hepatic artery with collagen fibers, causes substantial tumor necrosis. This procedure reportedly decreases tumor bulk of liver metastases from carcinoid tumors by more than 50% in as many as 60% of patients.35
- Adverse effects of embolization are frequent and may be severe (see Tumor Lysis Syndrome).
- Other surgical techniques, ablative but nonresective, include cryosurgery and percutaneous alcohol injections.
- For any patient with controlled carcinoid symptoms and heart involvement, cardiac surgery must be considered for symptomatic carcinoid heart disease and must be performed by an experienced team (including medical, surgical, and anesthesiology experts) in order to provide the best management of this condition.36,37
- For patients with silent disease and symptomatic carcinoid heart disease, valve replacement should be considered.
- Surgical resection can provide effective palliation in carefully selected patients. Debulking hepatic metastases may palliate systemic symptoms, and intestinal resection is highly effective in relieving symptoms of intestinal obstruction and ischemia.38 Palliative surgery may be associated with substantial morbidity, and the effects are often transient. However, a retrospective nonrandomized study suggests that patients with carcinoid heart disease who undergo hepatic resection have decreased cardiac progression and improved prognosis.39
Consultations
Consult with either a cardiologist or pneumologist for cardiac and respiratory assessment.
Diet
In patients with malignant carcinoid syndrome, diarrhea and weight loss are severe problems that need to be controlled.
- The major nutrients are absorbed easily and do not exacerbate the diarrhea, while most vegetables are very irritating.
- Patients with severe diarrhea should be careful to avoid dehydration or vitamin deficiency. Nicotinamide and niacin supplements are very useful and must be prescribed, along with potassium, magnesium, iron, and essential elements.
- Always recommend increased protein in the diet.
Activity
Mild (not stressful) physical activity is not harmful and is possible if desired. No intense physical activities are allowed.
Medication
Currently, somatostatin is rarely administered because of its poor half-life, and octreotide is considered the drug of choice worldwide for treating both carcinoids and related malignant syndromes. In patients with diffuse metastases, antiproliferative drugs may be useful for symptom palliation.40
Antisecretory/GI agents
These drugs are used to reduce blood levels of GH and IGF-I in patients with an inadequate response to surgery, radiation, and bromocriptine.
Octreotide (Sandostatin)
Acts primarily on somatostatin receptor subtypes II and V. Inhibits GH secretion and has many other endocrine and nonendocrine effects, including inhibition of glucagon, VIP, and GI peptides.
Adult
100 mcg SC tid/qid (most common effective dose); may administer direct IV over 5 min in emergency
Pediatric
Not established
May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers, and calcium channel blockers may need dosage adjustments
Documented hypersensitivity
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, GH), hypoglycemia or hyperglycemia may be observed; bradycardia, cardiac conduction abnormalities, and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism also may occur; caution with renal impairment; cholelithiasis may occur
Antineoplastic agents
These agents inhibit cell growth and proliferation.
Doxorubicin (Adriamycin)
Anthracycline antibiotic that can intercalate with DNA, affecting many DNA functions, including synthesis. Administered IV and distributes widely into bodily tissues, including the heart, kidneys, lungs, liver, and spleen. Does not cross blood-brain barrier and is excreted primarily in bile. May be helpful in symptom palliation for patients with progressive disease.
Adult
60-75 mg/m2 IV single dose q3-4wk; total dose not to exceed 550 mg/m2
Pediatric
Not established
Increased toxicity with cyclophosphamide, cyclosporine, mercaptopurine, verapamil, streptozocin, paclitaxel, and progesterone; phenobarbital decreases effect; decreased toxicity with digoxin; decreases phenytoin levels
Documented hypersensitivity; severe CHF; cardiomyopathy; preexisting myelosuppression; impaired cardiac function; complete cumulative doses of daunorubicin, doxorubicin, and idarubicin
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May produce severe local toxicity in irradiated tissues, even when the 2 therapies are not administered concomitantly; caution in patients who have received radiotherapy
Cardiomyopathy is a well-known characteristic of doxorubicin; monitor for drug-induced cardiomyopathy; mortality rate is higher than 50% once cardiomyopathy has developed
Reddish stain of urine (it is not blood in urine)
Streptozocin, streptozotocin (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
Increased nephrotoxicity with loop diuretics, aminoglycosides, or amphotericin B; increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents; enhanced hyperglycemia with corticosteroids
Documented hypersensitivity, renal disease
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Irreversible nephrotoxicity can occur; destabilizes control in patients with diabetes mellitus
Fluorouracil, 5-FU (Adrucil)
Fluorinated pyrimidine antimetabolite that inhibits thymidylate synthase (TS) and also interferes with RNA synthesis and function. Has some effect on DNA. Useful in symptom palliation for patients with progressive disease.
Adult
15 mg/kg/d IV continuous infusion (24 h) for 5 consecutive d
Pediatric
Not established
Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressive agents
Documented hypersensitivity, bone marrow suppression, and serious infection; topical administration contraindicated in pregnancy
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Nausea, oral and GI ulcers, depression of immune system, and hemopoiesis failure (bone marrow suppression) may occur; adjust dosage in renal impairment
Cisplatin (Platinol)
Inhibits DNA synthesis and thus cell proliferation by causing DNA crosslinks and denaturation of double helix. May help with symptom palliation for patients with progressive disease.
Adult
20-40 mg/m2 IV qd for 3-5 d q3wk; alternatively, 20-120 mg/m2 IV single dose q3wk
Pediatric
Not established
Increases toxicity of bleomycin and ethacrynic acid
Documented hypersensitivity, preexisting renal insufficiency, myelosuppression, hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Administer adequate hydration before and 24 h after cisplatin dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur
Etoposide (Toposar, VePesid)
Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in the late S or early G2 portion of the cell cycle. May help with symptom palliation for patients with progressive disease.
Adult
100 mg/m2 IV on days 3-5 in combination with other antineoplastic agents; dosage varies with protocol
Pediatric
Not established
May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in the cytotoxicity of tumor cells
Documented hypersensitivity; IT administration may cause death; breastfeeding
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Bleeding and severe myelosuppression may occur
Interferons
Interferons are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, and intralesionally.
Interferon-alpha, INF-alpha (Roferon-A, Intron-A)
Protein product manufactured by recombinant DNA technology. Mechanism of antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles. Therapeutic trials in selected patients.
Adult
Experimental therapeutic application; not established; administered SC; avoid intradermal injection
Pediatric
Not established
Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity
Documented hypersensitivity
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
Caution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, and compromised CNS; avoid breastfeeding
H1 antihistamines
These agents act by competitive inhibition of histamine at the H1 receptor. This mediates the wheal and flare reactions, bronchial constriction, mucous secretion, smooth-muscle contraction, edema, hypotension, CNS depression, and cardiac arrhythmias.
Cyproheptadine (Periactin)
Competitively inhibits H1 receptor, which mediates bronchial constriction, smooth-muscle contraction, edema, hypotension, CNS depression, and cardiac arrhythmias. Prevents histamine release in blood vessels and is more effective in preventing histamine response than in reversing it. May be useful in patients with syndromes sustained by histamine-producing tumors.
Adult
5-20 mg/d PO; not to exceed 0.5 mg/kg/d
Pediatric
Not established
Potentiates effects of CNS depressants; MAOIs may prolong and intensify anticholinergic and sedative effects
Documented hypersensitivity, narrow-angle glaucoma, stenosing peptic ulcer, symptomatic prostatic hypertrophy, bladder neck obstruction, pyloroduodenal obstruction, lower respiratory tract symptoms
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with a predisposition to urinary retention, history of bronchial asthma, increased intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension; may thicken bronchial secretions caused by anticholinergic properties and may inhibit expectoration and sinus drainage
H2-receptor antagonists
The combination of H1 and H2 antagonists may be useful in chronic idiopathic urticaria not responding to H1 antagonists alone. They may also be useful for itching and flushing in anaphylaxis, pruritus, urticaria, and contact dermatitis (IV).
Ranitidine (Zantac)
Competitive and reversible H2-receptor blockers. Highly selective antagonists that do not affect the H1 receptors and may be administered contemporary to H1-receptor antagonists. May be useful for treatment of severe itching, flushing, and urticaria.
Adult
150 mg PO qd/qid; not to exceed 600 mg/d; alternatively, 50 mg IV/IM q3-6h; not to exceed 400 mg/d
Pediatric
Not established
May decrease effects of ketoconazole and itraconazole; may alter serum levels of ferrous sulfate, diazepam, nondepolarizing muscle relaxants, and oxaprozin
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver impairment; if changes in renal function occur during therapy, consider adjusting dose or discontinuing treatment
Alpha2-adrenergic agonists
These agents improve the hemodynamic status by increasing myocardial contractility and heart rate, resulting in increased cardiac output. They are useful in reducing some symptoms of malignant carcinoid syndrome (eg, diarrhea, hypertension, tachycardia).
Clonidine (Catapres)
Stimulate alpha2 adrenoreceptors in brain stem, activating an inhibitory neuron, which, in turn, results in reduced sympathetic outflow. These effects result in a decrease in vasomotor tone and heart rate.
Adult
0.1-0.2 mg PO q8h
Pediatric
Not established
Tricyclic antidepressants inhibit hypotensive effects; coadministration of with beta-blockers may potentiate bradycardia; tricyclic antidepressants may enhance hypertensive response associated with abrupt clonidine withdrawal; hypotensive effects are enhanced by narcotic analgesics
Documented hypersensitivity
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
Caution in cerebrovascular disease, coronary insufficiency, sinus node dysfunction, and renal impairment; abrupt discontinuation may cause rebound hypertension
More on Malignant Carcinoid Syndrome |
| Overview: Malignant Carcinoid Syndrome |
| Differential Diagnoses & Workup: Malignant Carcinoid Syndrome |
 Treatment & Medication: Malignant Carcinoid Syndrome |
| Follow-up: Malignant Carcinoid Syndrome |
| Multimedia: Malignant Carcinoid Syndrome |
| References |
| « Previous Page | Next Page » |
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Further Reading
Keywords
malignant carcinoid syndrome, malignant carcinoid tumor, carcinoid tumors, cancer metastases, cancer metastasis, serotonin excess, neuroendocrine tumors, intestinal tumors, gastroenteropancreatic tumors, facial flushing, diarrhea, asthma
