Carcinoid tumors

Malignant carcinoid tumors, a symptom of carcinoid syndrome, presented a therapeutic challenge for many years until the introduction of interferon treatment in 1982 by Oberg and Eriksson [51]. They reported that 47 out of 111 patients (42%) treated with interferon- / (median dose of 6 mega-units (MU) of interferon-a, five... 

Ronnblom, L.E., Aim, G.V., and Oberg, K.E., Possible induction of systemic lupus erythematosus by interferon-alpha treatment in a patient with a malignant carcinoid tumor, J Intern Med., 227, 207,1990. 

Uses Pancreatic islet cell tumors carcinoid tumors Action DNA-DNA (int -strand) cross-linking DNA, RNA, protein synth inhibitor Dose Per protocol -1- in renal failure Caution w/ renal failure [D, /-] Contra w/ rotavirus vaccine, PRG Disp Inj SE N/V/D, duodenal ulcers, depression, X BM rare nephrotox (proteinuria azotemia dose related), hypophosphatemia dose limiting hypo-/hypCTglycemia inj site Rxns Interactions t Risk of nephrotox W/... 

No significant adverse effects were reported thus far. Carcinoid tumors were found in rats, probably... 

The prodrugs are unstable in the presence of acid and therefore must be administered as an enteric-coated preparation or as a buffered suspension. Pantoprazole is also available in an intravenous formulation. The most commonly reported side effects are diarrhea and headache. Hypergastrinemia has been noted as a reaction to the marked reduction in acid secretion. Gastric carcinoid tumors have developed in rats but not in mice or in human volunteers, even after long-term use. 

Streptozocin produces remission in 50 to 60% of patients with islet cell carcinomas of the pancreas. It is also useful in malignant carcinoid tumors. 

Stimulates granulocyte and macrophage production after chemotherapy Islet cell pancreatic carcinoma, malignant carcinoid tumor Breast cancer... 

Somatostatin has a very brief half-life in serum and is not useful clinically. An 8-amino acid analogue with 2 D-amino acids substituted for the naturally occurring L-amino acids is more stable, and monthly injections of a depot form of this analogue (octreotide, Sandostatin LAR) have several uses. Long-acting octreotide is used to treat acromegaly, as described earlier. It is also used to counteract unpleasant effects caused by overproduction of secreted bioactive substances produced by neuroendocrine tumors, including hyperinsulinemia from insulinomas and secretions from carcinoid tumors that cause severe diarrhea. Octreotide may also control severe diarrhea associated with AIDS that has not responded to other treatments. 

A patient with severe diarrhea as a result of a carcinoid tumor is a candidate for which of the following treatments ... 

C. Carcinoid tumors arise from neuroendocrine cells of the gut and secrete serotonin and gastrointestinal hormones, which activate the gastrointestinal tract and result in diarrhea. Most of these tumors have receptors for somatostatin, which inhibit secretion when activated, resulting in reduced activity of the gut. Octreotide is a stable analogue of... 

Although blood calcitonin levels are normally low, excessive levels have been found in association with medullary carcinoma of the thyroid and more rarely carcinoid tumors of the bronchus and stomach. Serum calcitonin levels are used to screen and monitor patients who have or are suspected of having medullary carcinoma of the thyroid. 

Unlabeled Uses Carcinoid tumors, chronic hepatitis B... 

Diarrhea IV (Sandostatin) Initially, 50-100 mcgqSh. May increase by lOOmcg/dose q48h. Maximum 500 meg q8h. Subcutaneous (Sandostatin) 50 meg 1-2 times a day. Carcinoid tumors IV, Subcutaneous (Sandostatin) 100-600 meg/day in 2-4 divided doses. IM (Sandostatin LAR Depot) 20mgq4wk. 

B. Indications and use Sandostatin is indicated to reduce blood levels of growth hormone and IGF-I (somatomedin-C) in acromegaly patients who have had inadequate response to or cannot be treated with surgical resection, pituitary irradiation, or bromocriptine mesylate at maximally tolerated doses. It is also indicated for the symptomatic treatment of patients with metastatic carcinoid tumors, where it suppresses or inhibits the severe diarrhea and flushing episodes associated with the disease, and for the treatment of the profuse watery diarrhea associated with VIP (vasoactive intestinal peptide)-secreting tumors (vipomas). 

Treatment of carcinoid and vasoactive intestinal peptide acromegaly (reduce blood levels of growth hormone), symptomatic treatment of metastatic carcinoid tumors, and profuse water diarrhea associated with intestinal tumors... 

Serotonin is an important neurotransmitter, a local hormone in the gut, a component of the platelet clotting process, and is thought to play a role in migraine headache. Serotonin is also one of the mediators of the signs and symptoms of carcinoid syndrome, an unusual manifestation of carcinoid tumor, a neoplasm of enterochromaffin cells. In patients whose tumor is not operable, a serotonin antagonist may constitute a useful treatment. 

Serotonin is metabolized by MAO, and the intermediate product, 5-hydroxyindoleacetaldehyde, is further oxidized by aldehyde dehydrogenase to 5-hydroxyindoleacetic acid (5-HIAA). In humans consuming a normal diet, the excretion of 5-HIAA is a measure of serotonin synthesis. Therefore, the 24-hour excretion of 5-HIAA can be used as a diagnostic test for tumors that synthesize excessive quantities of serotonin, especially carcinoid tumor. A few foods (eg, bananas) contain large amounts of serotonin or its precursors and must be prohibited during such diagnostic tests. 

Serotonin also constricts veins, and venoconstriction with increased capillary filling appears to be responsible for the flush that is observed after serotonin administration or release from a carcinoid tumor. Serotonin has small direct positive chronotropic and inotropic effects on the heart, which are probably of no clinical significance. However, prolonged elevation of the blood level of serotonin (which occurs in carcinoid syndrome) is associated with pathologic alterations in the endocardium (subendocardial fibroplasia), which may result in valvular or electrical malfunction. 

The actions of serotonin, like those of histamine, can be antagonized in several ways. Such antagonism is clearly desirable in those rare patients who have carcinoid tumor and may also be valuable in certain other conditions. 

The major clinical applications of cyproheptadine are in the treatment of the smooth muscle manifestations of carcinoid tumor and in cold-induced urticaria. The usual dosage in adults is 12-16 mg/d in three or four divided doses. It is of some value in serotonin syndrome, but because it is available only in tablet form, cyproheptadine must be crushed and administered by stomach tube in unconscious patients. 

Ketanserin (not available in USA) Competitive blockade at 5- 2 receptors Prevents vasoconstriction and bronchospasm of carcinoid syndrome Hypertension carcinoid syndrome associated with carcinoid tumor Oral duration 12-24 h Toxicity Hypotension Interactions Data not available... 

Of 12 patients (7 men, 5 women) with malignant mid-gut carcinoid tumors, median age 50 years, who received intramuscular octreotide pamoate 160 mg every 2 weeks for 2 months and then every month for 12 months, six developed unexplained episodic fever (51). No infection or cause was found. 

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