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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/31 22:52:33」(JST)

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Gemcitabine (pronunciation: jem-SITE-a-been) is a nucleoside analog used as chemotherapy. It is marketed as Gemzar by Eli Lilly and Company.

Pharmacology

Chemically gemcitabine is a nucleoside analog in which the hydrogen atoms on the 2' carbon of deoxycytidine are replaced by fluorine atoms.

As with fluorouracil and other analogues of pyrimidines, the triphosphate analogue of gemcitabine replaces one of the building blocks of nucleic acids, in this case cytidine, during DNA replication. The process arrests tumor growth, as only one additional nucleoside can be attached to the "faulty" nucleoside, resulting in apoptosis.

Another target of gemcitabine is the enzyme ribonucleotide reductase (RNR). The diphosphate analogue binds to RNR active site and inactivates the enzyme irreversibly. Once RNR is inhibited, the cell cannot produce the deoxyribonucleotides required for DNA replication and repair, and cell apoptosis is induced.^[1]

Administration

Gemcitabine is administered by the intravenous route, since it is extensively metabolized by the gastrointestinal tract. Dose ranges from 1-1.2 g/m² of body surface area according to type of cancer treated.^[2]

Indications

Gemcitabine is used in various carcinomas: non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer. It is being investigated for use in esophageal cancer, and is used experimentally in lymphomas and various other tumor types. Gemcitabine represents an advance in pancreatic cancer care^{[citation needed]}. It is also not as debilitating as some other forms of chemotherapy.

A study reported in the Journal of the American Medical Association in 2007 suggested that gemcitabine showed benefit in patients with pancreatic cancer who were felt to have successful tumor resections.^[3]

Gemcitabine became first line treatment for bladder cancer Stage 4 with metastases in combination with cisplatin after a study in 2000 with 405 patients showed similar efficacy but less toxicity compared to the former MVAC regimen.^[4] This new CG-regimen involves taking cisplatin on day 2 and taking gemcitabine on days 1, 8, and 15. In July 2006 the FDA approved gemcitabine for use with carboplatin in the treatment of advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based (e.g., carboplatin or cisplatin) therapy. Neutropenia was the most commonly reported adverse effect (90% of patients). Other serious adverse effects were mostly hematologic. Gemcitabine was recently also investigated for advanced cancer of the biliary tract and gallbladder and was found to have a modest effect on the tumor when combined with cisplatin (NEJM 2010).

GemCarbo chemotherapy for lung cancer

GemCarbo chemotherapy, consisting of a combination of gemcitabine and carboplatin, is used to treat several different types of cancer, but is most commonly used to treat lung cancer.^[5] GemCarbo chemotherapy is usually given as a day patient treatment, involving a blood test the day before, and the drugs are given by an infusion. The GemCarbo regimen is given as a 21-day cycle and on the first day of treatment the patient is given both the gemcitabine and carboplatin. On the same day of the following week (day eight) there is a drip of gemcitabine only. There then follows a rest period of two weeks which completes one cycle of chemotherapy. The next cycle of treatment is given after a rest period, which will be three weeks after the first injection. Usually 4–6 cycles of treatment are given over a period of 3–4 months and this makes up a course of treatment.

Side effects

Flu-like symptoms such as muscle pain, fever, headache, chills, and fatigue
Fever (within 6–12 hours of first dose)
Fatigue
Nausea (mild)
Vomiting
Poor appetite
Skin rash
Allergic reaction
Diarrhea
Weakness
Hair loss
Mouth sores
Difficulty sleeping
Shortness of breath

History

Gemcitabine was first synthesized in Larry Hertel's lab at Eli Lilly during the early 1980s.^[6] It was intended as an antiviral drug, but preclinical testing showed that it killed leukemia cells in vitro.^[6] It was first licensed in the UK in 1995.

References

^ N. M. F. S. A. Cerqueira, P. A. Fernandes, M. J. Ramos (2007). "Understanding ribonucleotide reductase inactivation by gemcitabine". Chemistry: A European Journal 13 (30): 8507–15. doi:10.1002/chem.200700260. PMID 17636467.
^ Chu E., DeVita V. T., "Physicians' Cancer Chemotherapy Drug Manual, 2007", Jones & Bartlett, 2007.
^ Oettle H, Post S, Neuhaus P et al. (January 2007). "Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial". JAMA 297 (3): 267–77. doi:10.1001/jama.297.3.267. PMID 17227978.
^ Von Der Maase, H; Hansen, SW; Roberts, JT; Dogliotti, L; Oliver, T; Moore, MJ; Bodrogi, I; Albers, P et al. (2000). "Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study". J Clin Oncol 18 (17): 3068–77. PMID 11001674.
^ Macmillan GemCarbo chemotherapy
^ ^a ^b Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 259. ISBN 0-471-89979-8.

External links

Gemzar.com

UpToDate Contents

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1. Overview of the management of bladder cancer in older adults
2. 非プラチナ製剤ベースの癌化学療法の神経学的合併症の概要 overview of neurologic complications of non platinum cancer chemotherapy
3. 進行性膵外分泌癌に対する化学療法 chemotherapy for advanced exocrine pancreatic cancer
4. 膀胱および泌尿器の転移性尿路上皮癌の治療 treatment of metastatic urothelial cancer of the bladder and urinary tract
5. 進行性胆管癌に対する全身療法 systemic therapy for advanced cholangiocarcinoma

English Journal

Multifunctional polymersomes for cytosolic delivery of gemcitabine and doxorubicin to cancer cells.

Nahire R1, Haldar MK1, Paul S2, Ambre AH3, Meghnani V1, Layek B1, Katti KS3, Gange KN4, Singh J1, Sarkar K5, Mallik S6.
Biomaterials.Biomaterials.2014 Aug;35(24):6482-97. doi: 10.1016/j.biomaterials.2014.04.026. Epub 2014 May 5.
Although liposomes are widely used as carriers of drugs and imaging agents, they suffer from a lack of stability and the slow release of the encapsulated contents at the targeted site. Polymersomes (vesicles of amphiphilic polymers) are considerably more stable compared to liposomes; however, they a
PMID 24797878

Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin.

Sudha T1, Yalcin M2, Lin HY3, Elmetwally AM1, Nazeer T4, Arumugam T5, Phillips P1, Mousa SA6.
Cancer letters.Cancer Lett.2014 Aug 1;350(1-2):25-33. doi: 10.1016/j.canlet.2014.04.016. Epub 2014 Apr 24.
Sulfated non-anticoagulant heparins (S-NACHs) might be preferred for potential clinical use in cancer patients without affecting hemostasis as compared to low molecular weight heparins (LMWHs). We investigated anti-tumor effects, anti-angiogenesis effects, and mechanisms of S-NACH in a mouse model o
PMID 24769074

Determination of six chemotherapeutic agents in municipal wastewater using online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry.

Rabii FW1, Segura PA2, Fayad PB1, Sauvé S3.
The Science of the total environment.Sci Total Environ.2014 Jul 15;487:792-800. doi: 10.1016/j.scitotenv.2013.12.050. Epub 2014 Jan 2.
Due to the increased consumption of chemotherapeutic agents, their high toxicity, carcinogenicity, their occurrence in the aquatic environment must be properly evaluated. An analytical method based on online solid-phase extraction coupled to liquid chromatography-tandem mass spectrometry was develop
PMID 24388503

Japanese Journal

症例報告ゲムシタビン単剤療法にて部分奏効を一時的にきたした血管肉腫の1例

森下加奈子,福田桂太郎,入來景悟 [他]
臨床皮膚科 = Japanese journal of clinical dermatology 68(8), 636-640, 2014-07
NAID 40020151083

症例報告 gemcitabine, nedaplatin併用化学療法が有用であった浸潤性尿管扁平上皮癌の1例

山田康隆,河野充,南村和宏 [他]
日本泌尿器科学会雑誌 = The Japanese journal of urology 105(3), 134-138, 2014-07
NAID 40020130079

局所進行膵癌に対する化学放射線療法および化学療法を中心とした治療成績 (特集胆膵癌の化学療法の最前線)

須藤研太郎,中村和貴,原太郎 [他]
消化器内科 58(6), 810-816, 2014-06
NAID 40020141142

Related Pictures

★リンクテーブル★

リンク元	「ゲムシタビン」「GEM」「GC regimen」
拡張検索	「gemcitabine hydrochloride」

「ゲムシタビン」

Gemcitabine
Systematic (IUPAC) name
	4-amino-1-(2-deoxy-2,2-difluoro-β-D-erythro-pentofuranosyl)pyrimidin-2(1H)-on
Clinical data
Trade names	Gemzar
AHFS/Drugs.com	monograph
Pregnancy; category	AU: D; US: D (Evidence of risk);
Legal status	AU: Pharmacy Only (S2); UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral, intravenous
Pharmacokinetic data
Protein binding	<10%
Biological half-life	Short infusions 32-94 minutes; for long infusions 245-638 minutes
Identifiers
CAS Registry Number	95058-81-4
ATC code	L01BC05
PubChem	CID: 60750
IUPHAR/BPS	4793
DrugBank	DB00441
ChemSpider	54753
UNII	B76N6SBZ8R
KEGG	D02368
ChEBI	CHEBI:175901
ChEMBL	CHEMBL888
Chemical data
Formula	C9H11F2N3O4
Molecular mass	263.198 g/mol
	SMILES c1cn(c(=O)nc1N)[C@H]2C([C@@H]([C@H](O2)CO)O)(F)F ;
	InChI InChI=1S/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m1/s1 ; Key:SDUQYLNIPVEERB-QPPQHZFASA-N ;
(what is this?) (verify)

　　[★]

英: gemcitabine GEM
化: 塩酸ゲムシタビン gemcitabine hydrochloride
商: ジェムザール
関: 抗悪性腫瘍薬

概念

代謝拮抗性抗悪性腫瘍薬である。
ゲムシタビンはデオキシシチジンの糖鎖の２′位の水素をフッ素に置換したヌクレオシド誘導体で、DNA合成が主に行われているS期に特異的な作用を示す。細胞内に取り込まれ三リン酸体に代謝され、デオキシシチジン三リン酸と競合してDNA 鎖に取り込まれ、DNAの合成を阻害する。

適応

非小細胞肺癌、膵癌、胆道癌、尿路上皮癌、手術不能又は再発乳癌、がん化学療法後に増悪した卵巣癌

参考

ジェムザール注射用200mg／ジェムザール注射用1g

http://www.info.pmda.go.jp/go/pack/4224403D1030_1_11/4224403D1030_1_11?view=body

「GEM」

　　[★]

「GC regimen」

　　[★]

適応

膀胱癌

「gemcitabine hydrochloride」

　　[★] ゲムシタビン gemcitabine。塩酸ゲムシタビン

[1] N. M. F. S. A. Cerqueira, P. A. Fernandes, M. J. Ramos (2007). "Understanding ribonucleotide reductase inactivation by gemcitabine". Chemistry: A European Journal 13 (30): 8507–15. doi:10.1002/chem.200700260. PMID 17636467.

[2] Chu E., DeVita V. T., "Physicians' Cancer Chemotherapy Drug Manual, 2007", Jones & Bartlett, 2007.

[pmid17227978-3] Oettle H, Post S, Neuhaus P et al. (January 2007). "Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial". JAMA 297 (3): 267–77. doi:10.1001/jama.297.3.267. PMID 17227978.

[4] Von Der Maase, H; Hansen, SW; Roberts, JT; Dogliotti, L; Oliver, T; Moore, MJ; Bodrogi, I; Albers, P et al. (2000). "Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study". J Clin Oncol 18 (17): 3068–77. PMID 11001674.

[5] Macmillan GemCarbo chemotherapy

[Sneader-6] Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 259. ISBN 0-471-89979-8.

匿名

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案内

案内

gemcitabine