Download Neuroendocrine Tumors

Systemic Therapy for
Gastroenteropancreatic (GEP)
Neuroendocrine Tumors and Lung
Carcinoid
The Medical Oncology Perspective
Nevena Damjanov, MD
Associate professor
Abramson Cancer Center of the
University of Pennsylvania
April 15, 2016
Neuroendocrine Tumors
 Relatively rare
 2-3 new cases/100,000 population per year
 Neuroendocrine tumors include
• Carcinoid tumors
• Pancreatic neuroendocrine tumors
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Functional and non functional islet cell tumors
Insulinomas
Glucagonomas
Gastrinomas
• Medullary carcinoma of the thyroid
• Paragangliomas
• Pheochromocytomas
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Where do neuroendocrine tumors come from?
 Neuroendocrine cells
• Secrete biogenic amines like neurons
• Secrete polypeptide hormones like endocrine
cells
 These cells populate the aerodigestive
system
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Lungs
Stomach
Pancreas
Intestines
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Most common locations of primary neuroendocrine tumors
Lungs
25%
Liver
Pancreas
Stomach
Small intestine
75%
Appendix
Colorectal
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Neuroendocrine Tumors
 Neuroendocrine tumors are classified
based on their site of origin and what, if
anything, they secrete
 Stomach
• Gastrin (gastrinoma)
 Pancreas islet cell tumors
• Insulin (insulinoma)
• Glucagon (glucagonoma)
 Appendix
• Carcinoid is the most common cancer of this
organ
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Neuroendocrine tumors
 Patients with functional NET have symptoms caused by
the oversecretion of hormones and other substances
 Patients with nonfunctional NET (70% of all NET) may
have no symptoms, or their symptoms may be caused
by tumor growth
• Intestinal obstruction from gastrointestinal NET
• Pain and bleeding
• Asthma from lung NET
• Chronic obstructive pulmonary disease and
pneumonia from lung NET
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Carcinoid Syndrome
 Most commonly seen in patients whose NET has
spread to the liver
 Diarrhea
 Flushing of the skin
 Wheezing/bronchospasm
 May cause carcinoid heart disease if not controlled
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Systemic Treatment
Goals of systemic treatment
 Control symptoms
 Control cancer spread
 Prolong survival
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Carcinoid Syndrome Symptom Control
Octreotide (Sandostatin) and lanreotide
(Somatuline)
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Injectable somatostatin analogs, bind receptors
on tumor cells
Effective in reducing hormone secretion, and
thus symptoms
Short and long acting formulations exist
 Sandostatin injections three times a day
 Sandostatin LAR once a month
 Somatuline Depot once a month
Even in patients without carcinoid syndrome,
octreotide/lanreotide may slow tumor growth
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Octreotide/Lanreotide
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Few side effects
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Mild nausea
Mild abdominal discomfort
Bloating
Loose stools
Fat malabsorption
Gallstones (common but usually asymptomatic)
Rare ileus (intestinal paralysis)
Side effects usually resolve after the first few
weeks of treatment
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Telotristat etiprate (LX1032)
 Telotristat etiprate is an investigational drug submitted
to the FDA for approval in 2016
 It comes in pill form
 Targets tryptophan hydroxylase
• This enzyme triggers excess serotonin production
 Unlike other treatments for carcinoid syndrome it does
not reduce the release of serotonin
 Telotristat etiprate reduces serotonin production within
tumor cells
 It has been shown to reduce the severity of diarrhea in
patients with carcinoid syndrome
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Foods That Can Aggravate Carcinoid Syndrome
 High amine containing foods
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aged cheese
pickled meat
broad beans
sauerkraut
soy sauce
 High fat foods
 Alcohol
 Large meals
 Caffeine, chocolate, tomato products
 Spices
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Chemotherapy
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Used in more aggressive tumors
Kills rapidly dividing cells
 Used when less toxic therapy is
ineffective
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No clear standard regimens
Small trials with few patients
 Disease with variable presentations
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Chemotherapy
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Single agent therapy
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Combinations
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Streptozocin, doxorubicin, 5-FU, etoposide
Dacarbazine IV → temozolomide by mouth
Taxanes, gemcitabine are ineffective
Streptozocin and 5-FU or doxorubicin
Temozolomide + thalidomide or capecitabine
(cap/tem)
In aggressive tumors (small cell cancers)
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Cisplatin/carboplatin + etoposide
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Targeted therapy
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Target molecular abnormalities seen
in cancers
Prevent cancer growth
 Prevent cancer spread
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Less toxic than conventional
chemotherapy
In other cancers, some are used with
conventional chemotherapy
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Afinitor (everolimus, RAD001)
 Administered in pill form (also available for suspension)
 FDA approved for kidney cancer, mBCa, and pNET
 It has shown efficacy in lung NETs
 Prevents cancer cells from dividing
 May kill cancer cells, as well
 Some patients taking Afinitor have tumor shrinkage,
while most patients have tumors that stop growing
 Combination therapy with octreotide is well tolerated
 May be especially effective in insulinomas
 Well tolerated
 Side effects include
• Fatigue, aphthous ulcers
• Low blood counts
• Increase in blood sugar, lipids
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Sutent (sunitinib)
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Administered in pill form
FDA approved for kidney cancer, GIST cancer, and
pNET
Prevents cancer cells from dividing
Some patients with NETs had tumor shrinkage
Many patients had tumor stabilization
Well tolerated
Side effects include
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Fatigue, diarrhea, thyroid disorders
Skin changes
Low blood counts
Increase in blood sugar, calcium
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Other Systemic Treatments with Some Activity in
Neuroendocrine tumors
 Bevacizumab
 Sorafenib
 Pazopanib
 Temsirolimus
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Conclusions
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Targeted therapy holds promise in
patients with neuroendocrine tumors
Multidisciplinary care is important
Patients with neuroendocrine tumors
may benefit from local and systemic
treatments, depending on the sites of
disease
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Summary - NET treatment
 Well differentiated NETs are rare, relatively
indolent malignancies.
 Care must be individualized.
 For many, watchful waiting may be most
appropriate initial maneuver.
 Indications for treatment are uncontrollable
symptoms due to
• Tumor bulk
• Hormone secretion
• Rapid/substantial progression of tumors while under
observation
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Summary - NET treatment
 Somatostatin analogues are typically first therapeutic
intervention.
 Once further therapy is needed, options exist
 Carcinoid tumors tend to grow slower and are more
resistant to chemotherapy and targeted therapies
 pNETs and lung NETs may be more responsive to
systemic therapy
 Old studies of chemotherapy agents are probably not
reliable.
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Summary - NET treatment
 Radiolabeled somatostatins are very promising
 Nonetheless, new treatments are needed.
 Please support clinical trials of new agents and new
treatment modalities.
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Thank you for your attention!
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