The reported world experience with liver transplant for carcinoid indicates that the outcome in general is as good but no better than that resulting from the best combination of multimodality treatment ( i.e. Octreotide/Sandostatin, Hepatic Artery Chemoembolization, Alpha interferon, tumor debulking by surgical excision, RFA, cryoablation, systemic chemotherapy and supportive measures). The rare exceptions when liver transplant is better are in those few cases with severe carcinoid syndrome unresponsive to Sandostatin with tumors restricted to the liver or in young patients with extensive tumors in the liver only and no tumors elsewhere.
15% of carcinoid patients cannot tolerate Sandostatin and it will not help them. There are additional medicines available which sometimes can make the Sandostatin tolerable or work. However, in some cases it must be abandoned and other forms of treatment should be tried. Somatuline Depot (lanreotide), a somatostatin analogue, by Tercica has been available in the United States since 2009.
The pump is a device in wide use for diabetics who need insulin. It usually is an elastic plastic ball which is filled with medicine under pressure and as it contracts very slowly it squeezes out the medicine slowly at a steady rate into a small plastic catheter attached to a needle which is correctly positioned under the skin.
In this article by Dr. Eugene Woltering (this is a technical article), he discusses the various methods for administering octreotide acetate drugs: http://www.carcinoid.org/medpro/docs/WoltPump2005.htm.
Here is some of what Dr. Woltering says about the pump: "Continuous subcutaneous infusions of octreotide acetate have been used by some physicians to take advantage of the rapid absorption of octreotide by the subcutaneous tissues. In this scenario the blood levels of octreotide begin to rise when the pump is turned on and continue to do so until the “steady state” is achieved—usually about 2-4 hours. Likewise, following the cessation of the subcutaneous infusion of octreotide, blood levels begin to fall and are back to insignificant levels after 6-8 hours (depending on dose used).Thus, the pump is ideal therapy for a patient who needs to be treated with high dose radiolabeled somatostatin analog therapy (like the 177 Lu, 90Y or 111In- based therapies) or has a negative Octreoscan in the past and wants to obtain the maximum sensitivity of this test. Another main advantage of pump- based therapy is the ability of a patient to increase or decrease the rate of infusion on a daily or weekly basis to control symptoms. "
Sandostatin when given in large doses (if OctreoScan is positive) along with alpha interferon (with which it works synergistically) causes tumor regression in 2/3 of the cases.
Cytoxic treatment is NOT pointless, especially after embolization treatment. It prolongs life. See article by Moertel et. al. The management of patients with advanced carcinoid tumors and islet cell carcinomas.
Sandostatin works in both ways.
Usually NOT. It may infrequently produce antibodies that make it less effective, but this is in only a very small minority of cases. In some other cases it becomes less effective AT THE SAME DOSAGE because the tumors are growing. In most cases it is better to take it early in the disease, especially if carcinoid syndrome is present and blood serotonin levels are elevated because it will prevent carcinoid heart disease and inhibit tumor growth as well as prevent carcinoid syndrome symptoms.
The main toxic side effect of streptozotocin is on the kidney and the 8th cranial nerve, the nerve that transmits hearing and the equilibrium function of the inner ear. Kidney damage is the more common side effect and is related to the dose and total amount of the drug given. Careful monitoring of the urine analysis and blood test and blood tests for kidney function before each treatment, with aborting treatment if the starts of abnormalities are seen can prevent any significant renal damage. This should be done in all cases. Therefore, no patient need suffer side effects from this drug. Similarly, periodic audiograms and checks of the patients vestibular function will present irreversible 8th nerve damage. Monitoring blood counts and adjusting dosage or withholding the drug will avoid serious suppression of the white blood cells. Cardiac damage is not a regular complication of this drug and would be extraordinary.
Radiotherapy is helpful for painful bone lesions.
Chemotherapy is effective in 1/3 of midgut carcinoids and in a larger percentage of foregut (including pancreatic) carcinoids. It is also more effective in atypical carcinoids. Sandostatin in large doses (300 mcg every 6-8 hours) often controls symptoms not responding to smaller doses. In addition, when combined with low dose alpha-Interferon, stabilizes or regresses tumor in up to three-quarters of cases.
All adrenaline (epinephrine) containing drugs must be avoided.
In general all carcinoid syndrome patients should be given a booster dose of regular Sandostatin just prior to any anesthesia, surgery or dentistry.
Morphine is okay for carcinoid patients but epinephrine is not since it can provoke carcinoid crisis. Epinephrine is sometimes used with local anesthesia to prolong the anesthesia by causing vasoconstriction. Novocain and other local anesthesia do come without epinephrine. Demerol and Fentazine can be used for post operative pain in people who are intolerant of morphine and Percocet.
DTIC is an anticancer drug also known as dacarbazine. Like many other anticancer drugs, its mode of action is not known, but it may act via one of the following three hypotheses:
1. Inhibiting DNA synthesis by acting as a purine analog.
2. Acting as an alkylating agent.
3. Interacting with SH group.
It is effective in 50% of carcinoid cases.
Dr. Woltering stands somewhat alone in his use of huge doses of Sandostatin. Based on his research observations he feels that very large doses inhibit carcinoid tumor cell growth whereas conventional doses inhibit hormone production, release and effect on target cells thereby relieving or preventing symptoms of the carcinoid syndrome. Except in a few cases of people who are intolerant of Sandostatin, the high doses usually cause no more side effects than do conventional doses. The expense is an important factor which can be the deciding factor in how the drug is used. Perhaps with more experience it will become clearer whether Dr. Woltering's conjecture is correct or incorrect.
In atypical carcinoid VP16 and Cisplatin is 67% effective. In typical carcinoid DTIC as a single agent has been reported effective in greater than 50%. Dr. Kjell Oberg (as well as myself through observation) reports greater than 60% effectiveness from CHRONIC treatment with large dosage octreotide along with small to moderate dosage alpha interferon. This combo (octreotide and alfa interferon) must be taken for at least 6 months before results are seen. Finally, leucovorin and LOW dose 5FU with streptozotocin given at frequent (weekly intervals) CHRONICALLY is effective in greater than 40% of cases. Note that if one chemotherapy program fails, the next one or two may be effective; i.e., failure to respond to one drug combo has no bearing on responsiveness to another. Aggressive treatment, rather than a wait-and-see approach, is better in the long run.
In general, radiotherapy for carcinoid tumor arising from the foregut is utilized only to treat painful metastatic bone metastases (in which instances it is usually effective), brain metastases, unresectable carcinoid of the larynx, unresectable carcinoid of the thymus and sometimes unresectable carcinoids of the lung. It is questionable whether radiotherapy is effective for lung carcinoid and it has the potential for injuring healthy parts of the adjacent lung by causing radiation pneumonitis and thereby impairing breathing further. It might be considered as a last option when all other treatments, including chemotherapy, have failed. I feel that there is no role for radiotherapy for gastric or pancreatic carcinoids.
Sometimes, not always, when a primary NET (neuroendocrine tumor) is removed and metastastatic tumors are already present, their growth is accelerated. However, sometimes the opposite occurs and their growth is related. These effects are thought to result from growth stimulating factor shifting to the metastases after their primary target is removed. On the other hand self-stimulating factors produced by the primary tumor also stimulate growth of metastases and these areas reduced by removing the primary tumor. It is a complicated situation which might be best handled by treating the tumor with tumor inhibiting medicines before and after surgery such as Sandostatin, alpha-interferon, chemotherapy, etc.
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