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Treatment |
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Gastro-entero-pancreatic neuroendocrine (GEP NE) tumours may be
treated with surgical resection of the tumour (local disease) and
regional nodal or hepatic metastases; somatostatin analogue therapy;
chemotherapy; and interferon therapy. Surgery may bring symptom
relief or even a cure, while synthetic forms of somatostatin, such
as octreotide, work at the site of the tumour and bind to sst-2/sst-5
receptors to regulate gastrointestinal hormone secretion and affect
tumour growth.18-20 Chemotherapy and radiation therapy are mainly
used for symptom relief. |
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Treating carcinoid tumours and carcinoid syndrome
Physicians often use a 2-pronged approach for carcinoid syndrome, beginning with surgery to remove the tumour or reduce its size, followed by treatment with somatostatin analogues, chemotherapy or interferons. A procedure known as hepatic embolization may be used to control cancer that has spread from a carcinoid tumour into the liver; it helps reduce symptoms by decreasing blood supply to the liver and starving tumour cells.
A second approach
involves treating symptoms with different medications:
- Heart disease-diuretics
- Wheezing-bronchodilators
- Hormone secretion inhibition-somatostatin analogues
- Diarrhoea and flushing-somatostatin analogues
Norton JA, Levin B, Jensen RT. Cancer of the endocrine system.
In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles
& Practice of Oncology. 4th ed. Philadelphia, PA: JB Lippincott;
1993;2:1333-1435. |
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Treating other types of GEP NE tumours
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VIPomas (Verner-Morrison syndrome):
First-line therapy for VIPomas aims to correct the profound hypokalaemia, dehydration and metabolic acidosis by replenishing fluids and electrolytes. Patients should be given up to 5 L of fluid and 350 mEq of potassium daily. Octreotide provides short- and long-term control of diarrhoea in most patients, and is effective in treatment-resistant diarrhoea and hypokalaemia.
The optimal treatment for VIPomas is surgical removal of the primary tumour. Surgery may result in a cure for patients who do not have metastases. Most VIPomas are malignant, but if the symptoms can be controlled, patients may live for many years with metastatic disease. In some patients, surgical resection in combination with chemotherapy may be useful.
Insulinomas (hypoglycaemic syndrome):
With malignant insulinoma, metastases may be found in the
surrounding lymph nodes and liver. If the tumour cannot be
localised before or during surgery (intra-operatively), it
may be removed through distal pancreatectomy. In many patients
with insulinomas, a long-acting somatostatin analogue reduces
hyperinsulinaemia and clinical symptoms.
Gastrinomas (Zollinger-Ellison syndrome):
In patients with gastrinomas, antisecretory medication such as a proton pump inhibitor is used to control gastric acid hypersecretion. If a patient cannot take this medication, a total gastrectomy is recommended. Surgery has been shown to yield a 30% 5-year cure rate, and is recommended in patients without liver metastases, MEN 1, or complicating medical conditions that may limit life expectancy. (Ninety-five percent of patients with gastrinomas have tumours.) Patients with metastatic disease may benefit from chemotherapy or octreotide, if chemotherapy fails. Glucagonomas:
Surgery is used to relieve the effects of glucagonomas or to reduce the size of the tumours. About one-third of patients can be cured by surgery following successful tumour localisation and assessment of metastatic disease. Octreotide can be used to improve symptoms and reduce octreotide levels. |
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Somatostatin analogue therapy
Somatostatin and somatostatin analogues are
proven first-choice medications for the control of symptoms that
occur from overproduction of hormones. These drugs work at the site
of GEP NE tumours to control their secretion, and in some cases
also their growthY. Octreotide is a synthetic form of somatostatin
used in the treatment of GEP NE tumours and carcinoid syndrome.
It blocks the release of bioactive substances from carcinoid tumours,
prolongs intestinal transit time and increases water and electrolyte
absorption, significantly reducing symptoms of diarrhoea and flushing.
A long-acting, slow-release form of octreotide (Sandostatin®
LAR® [octreotide/IM injection], Novartis Pharma AG) is available
for the treatment of symptoms of GEP NE tumours and carcinoid
syndrome. Administered intramuscularly once a month, it is as
efficacious as the standard formulation of octreotide (Sandostatin®
Injection, used 3 times daily) in suppressing symptoms due to
GEP NE tumours.21 Sandostatin® Injection has been used
as a safe and effective treatment for GEP NE tumours and carcinoid
syndrome for the past 10 years, and is the most prescribed22
and most studied23 medical therapy for GEP NE tumours.
(To date, octreotide has been listed in more than 5,000 scientific
publications.)
Another type of somatostatin analogue, lanreotide, is available
as an extended-release aqueous solution and a long-acting microparticle
formulation.25
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Efficacy of Sandostatin® LAR®
In patients with GEP NE tumours, Sandostatin®
LAR® suppresses diarrhoea and promotes water and electrolyte absorption.26-27
In addition, hormonal secretion is inhibited, peptide secretions
are reduced, splanchnic blood flow is decreased, and at the appropriate
doses, gastrointestinal transit time is prolonged.28-31
Lamberts SW et al. N Engl. J Med.1996;334:246-254
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Potent sst activation for enhanced biochemical and symptom control
Sandostatin® LAR® binds to 2 somatostatin
receptors that are expressed in the majority of GEP NE tumours-subtype-2
(sst-2 receptor) and subtype-5 (sst-5 receptor).32 These receptors
regulate gastrointestinal hormone secretion and can influence tumour
growth.
- Sandostatin® LAR® works at the site of the tumour and binds to sst-2/sst-5 receptors to regulate gastrointestinal hormone secretion and cell growth1-3
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- 80% of GEP/NE tumours express sst-2 and 77% express sst-54
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- Sandostatin® LAR® has 30% higher affinity for sst-2 than lanreotide SR5
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- Sandostatin® LAR® has 63% higher affinity for sst-5 than lanreotide SR5
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- More potent sst receptor activation and proven efficacy
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sst-2 |
sst-5 |
| Lanreotide |
0.54 |
17 |
| Octreotide |
0.38 |
6.3 |
Reference:
Bruns C et l. euro J Endocrinol. 2002;146:707-716.
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Proven efficacy to control debilitating symptoms
Sandostatin® LAR® effectively reduces GEP
NE and carcinoid tumour secretions, significantly reducing diarrhoea
and flushing associated with the overproduction of bioactive substances
from carcinoid tumours.
In patients with carcinoid syndrome,
Sandostatin® LAR® reduces the mean stool output from 4.0 stools/day
to 2.1 stools/day.33 The incidence of flushing episodes also is
reduced from 5.9 episodes/day to 0.6 episodes/day.34
The control of diarrhoea
and flushing begins after the first dose of Sandostatin® LAR®.35
*Data for lanreotide Autogel and lanreotide SR are not from comparative
studies
Sandostatin® LAR® has
a well-established safety profile, and most adverse events are
gastrointestinal as well as mild-to-moderate and short-term.36
The local pain on injection is generally mild-to-moderate and
short-term.37
(Please see the Novartis Core Labeling Text for more details)
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Patients Not Currently Receiving Octreotide38
For patients who were not previously treated
with subcutaneous (SC) Sandostatin®, it is recommended to start
with the administration of SC Sandostatin® at a dosage of 0.1 mg
3 times daily for a short period (approximately 2 weeks). Some patients
may require doses of up to 1500 mcg/day. The suggested daily dosage
for patients with VIPomas is 200 to 300 mcg in 2 to 4 divided doses
(range 150 to 750 mcg). The dosage may be adjusted on an individual
basis to control symptoms, but doses above 450 mcg/day are usually
not required.
The control of diarrhoea and flushing
begins after the first dose of Sandostatin® LAR®.35
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Patients Currently Receiving Octreotide39
Patients should be maintained on SC Sandostatin® for at least 2 weeks to assess side effects and determine tolerance. Patients who are thereafter considered "responders" and who tolerate the drug may be switched to LAR® Sandostatin® in the dosing scheme described directly below.
Patients who are currently receiving SC Sandostatin® can be switched directly to the slow-release formulation, using a dosage of 20 mg administered intragluteally at 4-week intervals for the initial 3 months, followed by dosage adjustment. Because of the need for serum octreotide to reach therapeutically effective levels following initial injection of the slow-release form of octreotide, patients should continue to receive SC octreotide for at least two weeks in the same dosage they were taking before the switch. An exacerbation of symptoms may occur if subcutaneous injections are not continued for this period. Some patients may require 3 to 4 weeks of combination SC Sandostatin®/Sandostatin® LAR® therapy.
After 3 months of receiving a 20-mg dosage of the slow-release form of octreotide, the dosage may be increased to 30 mg every 4 weeks if symptoms are not adequately controlled. (Despite good overall control of symptoms, patients with carcinoid tumours and VIPomas often experience periodic exacerbation of symptoms [regardless of whether they are being maintained on SC Sandostatin® or Sandostatin® LAR®]. During these periods, patients may be given SC Sandostatin® for a few days at the dose they were receiving prior to switching to Sandostatin® LAR®. When symptoms become controlled, the SC Sandostatin® can be discontinued.)
Patients who achieve good control on a 20-mg dose may have their dose lowered to 10 mg for a trial period. If symptoms recur, the dosage should then be increased to 20 mg every 4 weeks. Many patients can be satisfactorily maintained at a 10-mg dosage every 4 weeks. A dose of 10 mg is not recommended as a starting dose, however, because therapeutically effective levels of octreotide are reached more rapidly with a 20-mg dose. |
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