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CalderoaLU (talk | contribs) →Lutathera: Added information regarding Lutathera's approval, use, mechanism, studies, adverse reactions, and applications as well as information on GEP-NETs Tag: nowiki added |
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The company's lead product is LUTATHERA, a Lutetium Lu 177 dotatate <ref>[https://hemonc.org/wiki/Lutetium_Lu_177_dotatate_(Lutathera)</ref> labeled [[DOTA-TATE|somatostatin analogue peptide]], a theragnostic cancer product being developed to treat certain gastro-entero [[pancreatic]] [[neuroendocrine tumors]] ([[GEP-NET]]s). It selectively targets over-expressed somatostatin receptors while also giving off gamma emissions to allow physicians to visualize where in the body both the drug and the tumor are.
It was approved by the FDA in January 2018 for GEP-NET.<ref>[https://www.healio.com/hematology-oncology/gastrointestinal-cancer/news/online/%7B5e89833e-97c3-4a91-a2c8-88231a517b78%7D/fda-approves-lutathera-for-gastroenteropancreatic-neuroendocrine-tumors ''FDA approves Lutathera for gastroenteropancreatic neuroendocrine tumors'' Jan 2018]</ref>
== Approval ==
· Lutathera, also known as [[lutetium]] Lu 177 dotatate, is a target treatment drug for patients suffering from [[Neuroendocrine tumor|GEP-NETs]].<ref name=":0">{{Cite web|url=https://www.cancer.gov/news-events/cancer-currents-blog/2018/lutathera-fda-gastrointestinal-nets|title=FDA Approves New Treatment for Neuroendocrine Tumors|website=National Cancer Institute|language=en|access-date=2018-05-26}}</ref> Its approval for Advanced Accelerator Applications was announced on January 26, 2018 by the [[Food and Drug Administration|US Food and Drug Administration]].<ref name=":1">{{Cite web|url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm594043.htm|title=Press Announcements - FDA approves new treatment for certain digestive tract cancers|last=Commissioner|first=Office of the|website=www.fda.gov|language=en|access-date=2018-05-26}}</ref> Lutathera is most notable as the first FDA approved peptide receptor [[radionuclide]] therapy (PRRT) to combat GEP-NETs.<ref name=":2">{{Cite web|url=https://www.novartis.com/news/media-releases/advanced-accelerator-applications-receives-fda-approval-lutatherar-treatment-gastroenteropancreatic-neuroendocrine-tumors|title=Advanced Accelerator Applications Receives FDA Approval for Lutathera® for Treatment of Gastroenteropancreatic Neuroendocrine Tumors {{!}} Novartis|website=Novartis|language=en|access-date=2018-05-26}}</ref>
=== GEP-NETs ===
· [[Neuroendocrine tumor|GEP-NETs]] are rare groups of cancer that continue to proliferate, regardless of initial therapy treatments.<ref name=":0" /> They are present in areas affected by [[Pancreatic cancer|pancreatic]] or [[Gastrointestinal cancer|gastrointestinal cancers]]; specifically, the [[pancreas]], [[stomach]], [[intestines]], [[colon]] and [[rectum]].<ref name=":1" />
== Use ==
· Lutathera is used to combat pancreatic and gastrointestinal cancers that do not respond well to common [[Chemotherapy|chemo]]<nowiki/>therapeutical treatments; namely for patients with [[somatostatin]] receptor-positive GEP-NETs.<ref name=":0" /><ref name=":1" /> These receptors are commonly found on tumors located in the [[foregut]], [[midgut]], and [[hindgut]].<ref name=":3">{{Cite web|url=https://lutathera.com/|title=For Patients - Lutathera|website=Lutathera|language=en-US|access-date=2018-05-26}}</ref>
== Mechanism ==
· Lutathera is a radioactive drug comprised of a [[tyrosine]]-containing somatostatin analog Tyr3-octreotate (TATE) attached to the [[Chelation|chelating]] agent tetraazacyclododecanetetra-[[Acetic acid (medical use)|acetic acid]] (DOTA).<ref name=":4">{{Cite web|url=https://www.cancer.gov/publications/dictionaries/cancer-drug|title=NCI Drug Dictionary|website=National Cancer Institute|language=en|access-date=2018-05-26}}</ref> Attached to the [[DOTA-TATE|dotatate]] is the radioactive marker Lu-177, a [[radioisotope]].<ref name=":0" /> The dotatate binds to the GEP-NET positive somatostatin receptor cells commonly present on [[neuroendocrine]] tumors.<ref name=":0" /><ref name=":4" /> After binding to the receptor, Lutathera enters the cell and uses its radioactive property to damage DNA.<ref name=":0" /> This mechanism effectively triggers [[apoptosis]] of cancerous tumor cells. As a result, studies found that 16% of patients being treated with Lutathera experienced either complete or partial tumor shrinkage.<ref name=":0" />
== Studies ==
· FDA approval of Lutathera was ultimately supported by two clinical studies.<ref name=":1" /> NETTER-1, a Phase 3 study, was a randomized [[clinical trial]] which included patients with a severe form of somatostatin receptor-positive NETs.<ref name=":0" /><ref name=":2" /> The study compared Lutathera treatment with a standard dose of [[octreotide]]<nowiki/>d LAR against a high-dose of octreotide LAR.<ref name=":0" /> Researchers measured tumor growth after the course of the treatment, also known as [[progression-free survival]].<ref name=":1" /> The study concluded that patients who were treated with Lutathera lived substantially longer compared to those who only received the octreotide treatment.<ref name=":0" /> They experienced a 79% reduction in death and cancer progression.<ref name=":2" />
· The Netherlands study gathered several patients with somatostatin receptor-positive tumors, including patients with GEP-NETs.<ref name=":0" /> The study found that 16% of patients with GEP-NETs, who were treated with Lutathera, experienced complete or partial tumor shrinkage.<ref name=":0" /> As a result, a pre-planned interim overall survival analysis found that Lutathera treatment lead to a 48% reduction in risk of death.<ref name=":2" />
== Common Grade 3-4 Adverse Reactions<ref name=":0" /><ref name=":1" /><ref name=":2" /><ref name=":3" /> ==
{| class="wikitable"
|Common problems
|Symptoms/Reactions
|Percent of patients affected
|-
|
|Nausea
|5%
|-
|
|Vomiting
|7%
|-
|
|Hyperglycemia
|4%
|-
|
|Hypokalemia
|4%
|-
|Liver problems
|
|
|-
|
|Increased Gamma-Glutamyl Transferase
|20%
|-
|
|Elevated AST
|5%
|-
|
|Increased ALT
|4%
|-
|
|Tumor bleeding
|
|-
|
|Swelling (edema)
|
|-
|
|Tissue injury (necrosis)
|
|-
|Bone Marrow problems
|
|
|-
|
|Myelodysplastic syndrome
|2%
|-
|
|Acute leukemia
|1%
|-
|Kidney problems
|
|
|-
|
|Renal failure
|2%
|-
|Neuroendocrine hormonal crisis
|
|
|-
|
|Hypotension
|1%
|-
|
|Bronchospasm
|
|-
|Myelosuppression
|
|1%
|-
|
|Lymphopenia
|44%
|-
|
|Anemia
|
|-
|
|Thrombocytopenia
|
|-
|
|Leukopenia
|
|-
|
|Neutropenia
|
|-
|Cardiac problems
|
|
|-
|
|Myocardial infarction
|1%
|-
|
|Cardiac failure
|2%
|-
|Embryo-Fetal Toxicity
|
|
|-
|
|Causes harm to unborn fetuses
|
|-
|Temporary Infertility
|
|
|-
|
|May cause infertility
|
|}
== Advances ==
· Lutathera is a major technological advancement for the detection of tumors. [[Diagnostic imaging]] that relies on dotatates can now rely on Lutathera to locate somatostatin receptor-positive tumors by tagging them with its radioactive component.<ref name=":0" /> This tagging of tumors will allow them to become more visible during [[PET radiotracer|positron emission tomography]] (PET) scans.<ref name=":0" /> With LU-177 dotatates, more somatostatin receptor-positive GEP-NET patients can be identified for treatment of the disease.<ref name=":0" />
==Pipeline==
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