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a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/17 06:58:09」(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.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[1]

Medical uses

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.^[2]

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.^[3] 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 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).

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.^[4] 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.

Administration

Gemcitabine is administered by the intravenous route, since it is extensively metabolized by the gastrointestinal tract.^[5]

Side effects

^{[citation needed]}

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

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.^[6]

History

Gemcitabine was first synthesized in Larry Hertel's lab at Eli Lilly during the early 1980s.^[7] It was intended as an antiviral drug, but preclinical testing showed that it killed leukemia cells in vitro.^[7] It was first licensed in the UK in 1995.

References

^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ 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
^ Chu E., DeVita V. T., "Physicians' Cancer Chemotherapy Drug Manual, 2007", Jones & Bartlett, 2007.
^ 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.
^ ^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. 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
2. 進行性膵外分泌癌に対する化学療法 chemotherapy for advanced exocrine pancreatic cancer
3. 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
4. 進行性胆管癌に対する全身療法 systemic therapy for advanced cholangiocarcinoma
5. ドライバー変異が認められない進行非小細胞肺癌の初期マネージメントのための全身療法 systemic therapy for the initial management of advanced non small cell lung cancer without a driver mutation

English Journal

Long-term survival of a recurrent gallbladder carcinoma patient with lymph node and peritoneal metastases after multidisciplinary treatments: a case report.

Tomita K1, Takano K2, Shimazu M3, Okihara M4, Sano T5, Chiba N6, Kawachi S7.
Surgical case reports.Surg Case Rep.2016 Dec;2(1):12. doi: 10.1186/s40792-016-0135-8. Epub 2016 Feb 11.
BACKGROUND: Gallbladder carcinoma with peritoneal metastasis has a poor prognosis, with a median survival time of 4.8 months. We report the survival of a patient with gallbladder carcinoma with peritoneal metastasis for 7.6 months owing to treatment with tumor resection after chemoradiotherapy.CASE
PMID 26943688

Pulmonary hepatoid adenocarcinoma: report of a case.

Motooka Y1, Yoshimoto K2, Semba T3, Ikeda K4, Mori T5, Honda Y6, Iyama K7, Suzuki M8.
Surgical case reports.Surg Case Rep.2016 Dec;2(1):1. doi: 10.1186/s40792-016-0129-6. Epub 2016 Jan 8.
Hepatoid adenocarcinoma (HAC) is a rare neoplasm with aberrant hepatocellular differentiation. HAC occurs in extrahepatic organs such as the gastrointestinal tract, testes, ovaries, and lungs and frequently produces alpha-fetoprotein. A 69-year-old patient was diagnosed clinically with T2aN0M0, stag
PMID 26943677

Itraconazole therapy in a pancreatic adenocarcinoma patient: A case report.

Lockhart NR1, Waddell JA2, Schrock NE3.
Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners.J Oncol Pharm Pract.2016 Jun;22(3):528-32. doi: 10.1177/1078155215572931. Epub 2015 Feb 9.
OBJECTIVE: To report the case of a patient receiving itraconazole for the treatment of histoplasmosis and his subsequent reduction in pancreatic tumor size.CASE SUMMARY: A 64-year-old male was diagnosed with Stage III locally advanced unresectable pancreatic adenocarcinoma. The patient was administe
PMID 25670260

Japanese Journal

切除不能進行再発膵癌4 例に対する gemcitabine＋erlotinib 併用療法の経験:-特に副作用の抑制とコンプライアンスに関して-

日大医学雑誌 74(3), 106-108, 2015
NAID 130005120293

術後再発に対しCPT-11が著効した胆囊原発混合型腺神経内分泌癌の1例

日本消化器外科学会雑誌 48(7), 596-604, 2015
NAID 130005088270

切除不能膵癌に対するFOLFIRINOX治療の実際

膵臓 29(6), 885-891, 2014
NAID 130004873942

Related Pictures

★リンクテーブル★

リンク元	「ゲムシタビン」
関連記事	「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); ;
Routes of; administration	Oral, intravenous
Legal status
Legal status	AU: S2 (Pharmacy only); UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Protein binding	<10%
Biological half-life	Short infusions 32-94 minutes; for long infusions 245-638 minutes
Identifiers
CAS Number	95058-81-4
ATC code	L01BC05 (WHO)
PubChem	CID 60750
IUPHAR/BPS	4793
DrugBank	DB00441
ChemSpider	54753
UNII	B76N6SBZ8R
KEGG	D02368
ChEBI	CHEBI:175901
ChEMBL	CHEMBL888
Chemical data
Formula	C9H11F2N3O4
Molar 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 ;
(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

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[WHO2015E-1] "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.

[pmid17227978-2] 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.

[3] 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.

[4] Macmillan GemCarbo chemotherapy

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

[6] 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.

[Sneader-7] Sneader, Walter (2005). Drug discovery: a history. New York: Wiley. p. 259. ISBN 0-471-89979-8.

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案内

案内

gemcitabine hydrochloride