Frequently Asked Questions - Sandostatin

Xanthines and theobromines, as well as various foods and wines, contain substances that are provocative for carcinoid crisis and hence can interfere with the effectiveness of Sandostatin.  I do agree with Dr. Woltering in recommending carcinoid patients avoid these agents.

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.

Here are a few medical references dealing with the issue of efficacy of octreotide in control of tumor growth and/or reduction. There are more, but these are the initial ones that come to mind plus the 2009 published study. Feel free to print this article and show it to any physician who doubts the efficacy of octreotide (in this case Sandostatin):

The  reference published in 2009:
New Study First to Confirm Sandostatin LAR(R) Depot Controls Tumor Growth in Patients With Rare Gastrointestinal Tumors (Read full Text)
"In recent years, a growing body of evidence has suggested that Sandostatin LAR provides antitumor effects, but these are the first data to confirm this effect from a well-designed, prospective, placebo-controlled study," said David Epstein, President & CEO of Novartis Oncology.

EAST HANOVER, N.J., Jan. 13 /PRNewswire/ -- Sandostatin LAR(R) Depot (octreotide acetate suspension for injection) demonstrated antitumor benefit in patients with metastatic neuroendocrine tumors (NETs) of the midgut, according to interim data presented today at the 2009 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology.
- Data show significant 66% reduction in risk of disease progression versus placebo
- Sandostatin LAR more than doubled time without tumor growth for a median of 14 months compared to six months on placebo
- Results support Sandostatin LAR as first treatment after surgery in certain patients with newly diagnosed neuroendocrine tumors (NETs)

Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients With Metastatic Neuroendocrine Midgut Tumors: A Report From the PROMID Study Group (Read Full Text)

Abstract:

Purpose: Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.

Patients and Methods: Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.

Results: Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18)

Conclusion: Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
 
Carcinoid tumor regression with high-dose octreotide acetate: a patient report.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract

Efficacy of octreotide in the regression of a metastatic carcinoid tumor despite negative imaging with In-111-pentetreotide (Octreoscan). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9626790&dopt=Abstract

Also in a very impressive and comprehensive review:

Carcinoid tumors and the carcinoid syndrome. Jensen, R.T., Norton, JA In: DeVita, VT Jr., Hellman, S, Rosenberg S eds. Cancer; Principles Practice of Oncology, 5th ed. Philadelphia, P Lippincott-Raven; 1997; 2:1704-1723.
It is stated on page 1718: octreotide may have a tumoriostatic effect, stabalizing the extent of metastatic disease and prolonging survival (with three references).

In Metastatic carcinoid tumors and the malignant carcinoid syndrome, Kvols, LK, Reubi, JC, the authors state: Even though objective tumor regression was unusual, previously progressive disease often became stable and this seems to have translated into favorable long-term survival.
Refer to: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8323761&dopt=Abstract

And to quote from Somatostatin analogue octreotide and inhibition of tumor growth in metastatic endocrine gastroenteropancreatic tumors. Arnold, R, Trautmann, ME, Creutzfeldt, W, Benning R, Benning, M, Neuhaus, C, Jurgensen, R, Stein, K. Schafer, H, Bruns, C, Dennler, H.J. The results suggest that octreotide inhibits tumor growth in patients with metastases endocrine GEP tumors. The antiproliferative effect is, at least in some patients, long lasting.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=8675099&dopt=Abstract

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.

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.

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.

An OctreoScan can very occasionally show a carcinoid before CT scan or chemistries indicate its presence, but this situation is very infrequent. Visually it is used to help locate a tumor when chemistries show it is present and CT scan doesn't image it. Also when CT scan is positive the OctreoScan may show additional sites of the tumor not seen on CT.

Finally even when tumor is seen on a CT scan and chemistries are positive, the OctreoScan is useful because a positive result indicates the presence of SST2 receptors in the tumor and that means the patient will most likely respond well to treatment with Sandostatin and also has a better prognosis than does the patient with carcinoid tumor but a negative OctreoScan.

An OctreoScan is fairly straightforward. While it cannot give an indication as to tumor size, it can indicate the extent of disease metastasis and show possible loci for tumors which may or may not have been suspected. Essentially what happens is this: about 4 to 24 hours prior to scanning, a Nuclear tag (about 6 milliCuries) piggybacked onto a somatostatin analog (like Sandostatin) is injected.

This tag is then taken up by any tissue exhibiting a type two receptor. Usually you find type two receptors in carcinoid cancers, liymphomas, some breast cancers and so on. The body of the person is then scanned at 24, 48 and possibly 72 hours or whenever the oncologist and radiologist deem it beneficial. The tag being tumor-specific will cause any tissue with the requisite receptors to light up on the scan film. The test is sort of go or no-go.

Most carcinoid tumors have the receptors and light up the film; about 2 percent of tumors do not have the receptors and thus do not show up. If the patient is on a somatastatin medication such as Sandostatin, the receptors will be blocked and the tumors will not show up. Sandostatin has to be stopped about 3 days prior to scanning for an accurate test to be performed.

The OctreoScan is a test which images 85% of carcinoid tumors but is not the best way to show their growth. It does indicate the potential usefulness of Sandostatin (octreotide) treatment when a tumor lights up on the OctreoScan.