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Khác biệt giữa bản sửa đổi của “Oxaliplatin”

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==Phát hiện và cấu trúc==
Oxaliplatin được tìm ra vào năm 1976 tại Đại học [[Nagoya City University]] nhờ giáo sư Yoshinori Kidani, được cấp bằng sáng chế U.S. Patent 4,169,846 vào năm 1979. Oxaliplatin được đưa ra cấp phép cho [[Debiopharm]] và sử dụng điều trị ung thư trực tràng. Debio cấp phép cho [[Sanofi-Aventis]] vào 1994. Eloxatin được châu Âu chấp thuận vào năm 1996 (đầu tiên là ở Pháp) và [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) chấp nhận vào năm 2002.
 
The compound features a [[square planar]] platinum(II) center. In contrast to [[cisplatin]] and [[carboplatin]], oxaliplatin features the [[bidentate]] ligand [[1,2-diaminocyclohexane]] in place of the two [[Denticity|monodentate]] ammine [[ligand]]s. It also features a bidentate oxalate group.
 
== Cơ chế tác dụng ==
The cytotoxicity of platinum compounds is thought to result from inhibition of DNA synthesis in cancer cells.
In vivo studies showed that Oxaliplatin has anti-tumor activity against colon carcinoma through its (non-targeted) [[cytotoxic]] effects.
 
Oxaliplatin functions by forming both inter- and intra- strand cross links in DNA.<ref>{{chú thích tạp chí|last=Graham|first=Joanne|coauthors=Mushin, Mohamed; Kirkpatrick, Peter|title=Oxaliplatin|journal=Nature Reviews Drug Discovery|year=2004|month=January|volume=3|issue=1|pages=11–2|doi=10.1038/nrd1287|pmid=14756144}}</ref> Cross links in DNA prevent DNA replication and transcription, resulting in cell death.
 
== Clinical use ==
Oxaliplatin is typically administered with [[fluorouracil]] and [[leucovorin]] in a combination known as [[FOLFOX]] for the treatment of [[colorectal cancer]]. Oxaliplatin is marketed by [[Sanofi-Aventis]] under the trademark '''Eloxatin''' or by [[Medac]] GmbH under the trademark '''Oxaliplatin Medac'''. There are generic equivalents on the market now<ref>Generic Oxaliplatin Approved</ref> Oxaliplatin has been compared with other platinum compounds (Cisplatin, Carboplatin) in advanced cancers (gastric, ovarian).
 
=== Advanced colorectal cancer ===
In clinical studies, Oxaliplatin by itself has modest activity against advanced colorectal cancer.<ref>{{chú thích tạp chí | author = Becouarn Y, Ychou M, Ducreux M ''et al.'' | year = 1998 | title = Phase II trial of oxaliplatin as first-line chemotherapy in metastatic colorectal cancer patients. Digestive Group of French Federation of Cancer Centers | url = | journal = J Clin Oncol | volume = 16 | issue = 8| pages = 2739–44 | pmid = 9704726 }}</ref> It has been extensively studied in combination with Fluorouracil and Folinic Acid (a combination known as FOLFOX). When compared with [[fluorouracil]] and [[folinic acid]] administered according to the "De Gramont regimen" there was no significant increase in overall survival with the FOLFOX regimen (specifically, FOLFOX4), but [[progression-free survival]], the primary end-point of the phase III randomized trial, was improved with FOLFOX.<ref>{{chú thích tạp chí | author = De Gramont A, Figer A, Seymour M ''et al.'' | year = 2000 | title = Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer | url = | journal = J Clin Oncol | volume = 18 | issue = 16| pages = 2938–47 | pmid = 10944126 }}</ref>
 
=== Adjuvant treatment of colorectal cancer ===
After the curative resection of colorectal cancer, chemotherapy based on Fluorouracil and folinic acid reduces the risk of relapse. The benefit is clinically relevant when cancer has spread to locoregional lymph nodes (stage III, Dukes C). The addition of Oxaliplatin improves relapse-free survival, but data on overall survival have not yet been published ''in extenso''. <br />
When cancer has '''not''' spread to the locoregional lymph nodes (stage II, Dukes B) the benefit of chemotherapy is marginal and the decision on whether to give adjuvant chemotherapy should be carefully evaluated by discussing with the patient the realistic benefits and the possible toxic side effects of treatment. This is even more relevant when the oncologist proposes treatment with Oxaliplatin.
 
== Adverse effects ==
Side-effects of oxaliplatin treatment can potentially include:
* [[Neurotoxicity]] leading to [[chemotherapy-induced peripheral neuropathy]], a progressive, enduring and often irreversible tingling numbness, intense pain and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs, often with deficits in [[proprioception]].<ref name=pasetto>{{chú thích tạp chí | pmid = 16806962 | doi=10.1016/j.critrevonc.2006.01.001 | volume=59 | issue=2 | title=Oxaliplatin-related neurotoxicity: how and why? | year=2006 | month=August | author=Pasetto LM, D'Andrea MR, Rossi E, Monfardini S | journal=Crit. Rev. Oncol. Hematol. | pages=159–68}}</ref>
* [[Fatigue (physical)|Fatigue]]
* [[Nausea]], [[vomiting]], and/or [[diarrhea]]
* [[Neutropenia]] (low number of a type of white blood cells)
* [[Ototoxicity]] (hearing loss)
* [[Extravasation]] if Oxaliplatin leaks from the infusion vein it may cause severe damage to the connective tissues.
* [[Hypokalemia]] (low blood potassium), which is more common in women than men<ref name=chay>{{chú thích tạp chí | pmid = 20092386 | doi=10.3109/02841860903464015 | volume=49 | issue=4 | title=An association between transient hypokalemia and severe acute oxaliplatin-related toxicity predominantly in women | year=2010 | month=May | author=Chay WY, Chew L, Yeoh TT, Tan MH | journal=Acta Oncol | pages=515–7}}</ref>
 
In addition, some patients may experience an [[allergy|allergic reaction]] to platinum-containing drugs. This is more common in women.<ref name=chay/>
 
Oxaliplatin has less ototoxicity and [[nephrotoxicity]] than cisplatin and carboplatin.<ref name=pasetto/>
 
== Patent information ==
Eloxatin is covered by patent numbers 5338874 (Expiry Apr 07,2013), 5420319 (Expiry Aug 08,2016), 5716988 (Expiry Aug 07,2015) and 5290961 (Expiry Jan 12, 2013) (see Electronic Orange Book patent info for Eloxatin).<ref name="Appl No 021759">Orange Book. accessdata.fda.gov. URL: [http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021759&Product_No=001&table1=OB_Rx http://www.accessdata.fda.gov/scripts/cder/ob/docs/patexclnew.cfm?Appl_No=021759&Product_No=001&table1=OB_Rx]. Accessed on: July 22, 2007.</ref> Exclusivity code I-441, which expired on Nov 04, 2007, is for use combination with infusional 5-FU/LV for adjuvant treatment stage III colon cancer patients who have undergone complete resection primary tumor-based on improvement in disease free survival with no demonstrated benefit overall survival after 4 years. Exclusivity code NCE, New Chemical Entity, expired on Aug 09, 2007.<ref name="Appl No 021759"/>
 
==Tham khảo==
{{tham khảo|2}}
 
==Đọc thêm==
* {{chú thích tạp chí | jillauthor = Graham J, Mushin M, Kirkpatrick P | title = Oxaliplatin | journal = Nat Rev Drug Discov | volume = 3 | issue = 1 | pages = 11–2 | year = 2004 | pmid = 14756144 | url=http://www.dresources.com/nature/ntr_0104.pdf | format=PDF | doi=10.1038/nrd1287 | author=Graham J, Mushin M, Kirkpatrick P}}▼
 
==Liên kết ngoài==
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* [http://www.cancer.gov/cancertopics/druginfo/oxaliplatin NCI Drug Information Summary on Oxaliplatin]
 
[[Thể loại:AmmineHợp complexeschất Platin]]▼
==Additional sources==
[[Thể loại:PlatinumPhức compoundsamin]]▼
▲* {{chú thích tạp chí | jill = Graham J, Mushin M, Kirkpatrick P | title = Oxaliplatin | journal = Nat Rev Drug Discov | volume = 3 | issue = 1 | pages = 11–2 | year = 2004 | pmid = 14756144 | url=http://www.dresources.com/nature/ntr_0104.pdf | format=PDF | doi=10.1038/nrd1287 | author=Graham J, Mushin M, Kirkpatrick P}}
 
{{Chemotherapeutic agents}}
{{Platinum compounds}}
 
[[Thể loại:Alkylating antineoplastic agents]]
[[Thể loại:Coordination compounds]]
▲[[Thể loại:Platinum compounds]]
▲[[Thể loại:Ammine complexes]]
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