関: カペシタビン capecitabine

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/26 14:15:41」(JST)

wiki en

Capecitabine (INN) /keɪpˈsaɪtəbiːn/ (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of numerous cancers.^[1] Capecitabine is a prodrug that is enzymatically converted to 5-fluorouracil (5-FU) in the body.^[2]

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.^[3]

Medical uses

It is used in the treatment of the following cancers:^[1]^[2]^[4]

Colorectal cancer (either as neoadjuvant therapy with radiation, adjuvant therapy or for metastatic cases)
Breast cancer (metastatic or as monotherapy/combotherapy; this is licensed as a second-line treatment in the UK)
Gastric cancer (off-label in the US; this is a licensed indication in the UK)
Oesophageal cancer (off-label in the US)

Adverse effects

Adverse effects by frequency:^[5]^[6]^[7]^[8]

Very common (>10% frequency)

Appetite loss
Diarrhea
Vomiting
Nausea
Stomatitis
Abdominal pain
Fatigue
Weakness
Hand-foot syndrome^[9]
Oedema
Fever
Pain
Headache
Hair loss
Dermatitis
Indigestion
Shortness of breath
Eye irritation
Myelosuppression^{[Note 1]}

Notes on adverse effects:

^ Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia

Contraindications

Contraindications include:^[7]

History of hypersensitivity to fluorouacil, capecitabine or any of its excipients.
Patients with DPD deficiency (see Pharmacogenetics)
Pregnancy and lactation
Patients with pre-existing blood dyscrasias
Patients with severe hepatic impairment or severe renal impairment
Treatment with sorivudine or its chemically related analogues, such as brivudine

Drug interactions

Drugs it is known to interact with includes:^[7]

Sorivudine or its analogues, such as, brivudine.
Allopurinol as it decreases the efficacy of 5-FU.
CYP2C9 substrates, including, warfarin and other coumarin-derivatives anticoagulants
Phenytoin, as it increases the plasma concentrations of phenytoin.
Calcium folinate may enhance the therapeutic effects of capecitabine by means of synergising with its metabolite, 5-FU. It may also induce more severe diarrhoea by means of this synergy.^[1]

Pharmacogenetics

The dihydropyrimidine dehydrogenase (DPD) enzyme is responsible for the detoxifying metabolism of fluoropyrimidines, a class of drugs that includes capecitabine, 5-fluorouracil and tegafur.^[10] Genetic variations within the DPD gene (DPYD) can lead to reduced or absent DPD activity, and individuals who are heterozygous or homozygous for these variations may have partial or complete DPD deficiency; an estimated 0.2% of individuals have complete DPD deficiency.^[10]^[11] Those with partial or complete DPD deficiency have a significantly increased risk of severe or even fatal drug toxicities when treated with fluoropyrimidines; examples of toxicities include myelosuppression, neurotoxicity and hand-foot syndrome.^[10]^[11] The FDA-approved drug label for capecitabine states that the drug is contraindicated in patients with known DPD deficiency.^[5]

Mechanism of action

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

[[File:

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

[[

]]

|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]

File:FluoropyrimidineActivity_WP1601.png

Fluorouracil (5-FU) Activity edit

^ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Capecitabine is metabolised to 5-FU which in turn is a thymidylate synthase inhibitor, hence inhibiting the synthesis of thymidine monophosphate (ThMP), the active form of thymidine which is required for the de novo synthesis of DNA.^[2]

References

^ ^a ^b ^c Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
^ ^a ^b ^c "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014.
^ "www.who.int" (PDF).
^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.
^ ^a ^b "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Retrieved 25 January 2014.
^ "Capecitabine Teva : EPAR - Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Retrieved 25 January 2014.
^ ^a ^b ^c "Capecitabine 150mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Retrieved 25 January 2014.
^ "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Retrieved 25 January 2014.
^ Reddening, swelling, numbness and desquamation on palms and soles
^ ^a ^b ^c Caudle, KE; Thorn, CF; Klein, TE; Swen, JJ; McLeod, HL; Diasio, RB; Schwab, M (December 2013). "Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.". Clinical pharmacology and therapeutics 94 (6): 640–5. doi:10.1038/clpt.2013.172. PMID 23988873.
^ ^a ^b Amstutz, U; Froehlich, TK; Largiadèr, CR (September 2011). "Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity.". Pharmacogenomics 12 (9): 1321–36. doi:10.2217/pgs.11.72. PMID 21919607.

External links

Xeloda.com (patient information, tools, and resources)
OralChemo Advisor (patient information)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 成人における抗癌剤の投与 dosing of anticancer agents in 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. 高齢患者およびperformance statusのスコアが低い患者における転移性大腸癌に対する治療 therapy for metastatic colorectal cancer in elderly patients and those with a poor performance status
4. Adjuvant therapy for resected stage III (node-positive) colon cancer
5. 女性の転移性乳癌に対する全身療法：化学療法 systemic treatment of metastatic breast cancer in women chemotherapy

English Journal

Isorhamnetin augments the anti-tumor effect of capeciatbine through the negative regulation of NF-κB signaling cascade in gastric cancer.

Manu KA1, Shanmugam MK1, Ramachandran L1, Li F1, Siveen KS1, Chinnathambi A2, Zayed ME2, Alharbi SA2, Arfuso F3, Kumar AP4, Ahn KS5, Sethi G6.
Cancer letters.Cancer Lett.2015 Jul 10;363(1):28-36. doi: 10.1016/j.canlet.2015.03.033. Epub 2015 Mar 28.
Development of drug resistance to standard chemotherapy is a common phenomenon that leads to poor prognosis in patients. Thus, novel agents that can attenuate chemoresistance are urgently needed. Therefore, we analyzed whether isorhamnetin (IH), a 3'-O-methylated metabolite of quercetin, can enhance
PMID 25827070

Impact of hand-foot skin reaction on treatment outcome in patients receiving capecitabine plus erlotinib for advanced pancreatic cancer: A subgroup analysis from AIO-PK0104.

Kruger S1, Boeck S, Heinemann V, Laubender RP, Vehling-Kaiser U, Waldschmidt D, Kettner E, Märten A, Winkelmann C, Klein S, Kojouharoff G, Gauler TC, Fischer von Weikersthal L, Clemens MR, Geissler M, Greten TF, Hegewisch-Becker S, Modest DP, Stintzing S, Haas M.
Acta oncologica (Stockholm, Sweden).Acta Oncol.2015 Jul;54(7):993-1000. doi: 10.3109/0284186X.2015.1034877. Epub 2015 Apr 30.
BACKGROUND: Drug-induced skin toxicity may correlate with treatment efficacy in cancer patients receiving chemotherapy or biological agents. The correlation of the capecitabine-associated hand-foot skin reaction (HFS) on outcome parameters in pancreatic cancer (PC) has not yet been investigated.METH
PMID 25924969

Paraneoplastic thrombocytosis independently predicts poor prognosis in patients with locally advanced pancreatic cancer.

Chadha AS1, Kocak-Uzel E, Das P, Minsky BD, Delclos ME, Mahmood U, Guha S, Ahmad M, Varadhachary GR, Javle M, Katz MH, Fleming JB, Wolff RA, Crane CH, Krishnan S.
Acta oncologica (Stockholm, Sweden).Acta Oncol.2015 Jul;54(7):971-8. doi: 10.3109/0284186X.2014.1000466. Epub 2015 Jan 22.
BACKGROUND AND AIMS: Platelets are believed to promote tumor growth and metastasis but their prognostic role in locally advanced pancreatic cancer (LAPC) remains largely unknown. We assessed whether pretreatment platelet counts independently predict survival outcomes in patients with LAPC treated wi
PMID 25608822

Japanese Journal

Team Approach for XELOX+Bevacizumab Therapy

松岡宏,前田耕太郎,花井恒一,佐藤美信,升森宏次,小出欣和,勝野秀稔,野呂智仁,本多克行,塩田規帆,遠藤智美,松岡伸司
日本大腸肛門病学会雑誌 66(1), 7-12, 2013
… This report describes the effectiveness of adverse event management and the improvement of ingestion compliance by the team of doctors, nurses, and pharmacists.<BR>The rate of Hand Foot Syndrome grade 2/3 in a domestic phase I/II study JO19380 was 17.2%/1.7% respectively, while that in our study was 13.2%/0%.<BR>The relative dose intensity of six courses was 89.2% (L-OHP) and 91.0% (XELODA), respectively. …
NAID 130003369826

Clinical Efficacy of Capecitabine and Cyclophosphamide (XC) in Patients with Metastatic Breast Cancer

Shien Tadahiko,Doihara Hiroyoshi,Nishiyama Keiko,Masuda Hiroko,Nogami Tomohiro,Ikeda Hirokuni,Taira Naruto
Acta Medica Okayama 65(4), 231-237, 2011-08
… Combined low-dose therapy of oral capecitabine (Xeloda) and cyclophosphamide (XC) has been demonstrated to be useful for long-term control of lesions in patients with metastatic breast cancer (MBC) and is aimed at symptomatic alleviation and prolongation of survival. …
NAID 80021895205

ヒト大腸癌細胞株(DLD/1)においてCapecitabine(Xeloda)と2-methoxyestradiol(2-ME2, Panzem)を用いた化学放射線療法が及ぼす抗腫瘍効果についての基礎的検討

仲田栄子,高井良尋,小川芳弘 [他]
放射線生物研究 45(1), 88-95, 2010-03
NAID 40017079926

Related Pictures

Xeloda – Treatment for Metastatic Colorectal Cancer - Drug Development Technology Xeloda. 150 mg. 60 tablets Xeloda Oral Tablet Drug Information, Side Effects, Faqs XELODA 150 Pill - Xeloda 150 mg Xeloda 500mg Tablets - Xeloda 500mg Tablets Exporter, Manufacturer, Distributor Xeloda Filmtabl 500 Mg 120 Stk in der Adler Apotheke Xeloda avastin side effects - Answers on HealthTap XELODA 500 Pill - Xeloda 500 mg

★リンクテーブル★

リンク元

「カペシタビン」

Capecitabine
Systematic (IUPAC) name
	Pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
Clinical data
Trade names	Xeloda
AHFS/Drugs.com	monograph
MedlinePlus	a699003
Pregnancy; category	AU: D; US: D (Evidence of risk);
Legal status	AU: Prescription Only (S4); UK: Prescription-only (POM); US: ℞-only;
Routes of; administration	Oral
Pharmacokinetic data
Bioavailability	Extensive
Protein binding	< 60%
Metabolism	Hepatic, to 5'-DFCR, 5'-DFUR (inactive); neoplastic tissue, 5'-DFUR to active fluorouracil
Biological half-life	38–45 minutes
Excretion	Renal (95.5%), faecal (2.6%)
Identifiers
CAS Registry Number	154361-50-9
ATC code	L01BC06
PubChem	CID: 60953
IUPHAR/BPS	6799
DrugBank	DB01101
ChemSpider	54916
UNII	6804DJ8Z9U
KEGG	D01223
ChEBI	CHEBI:31348
ChEMBL	CHEMBL1773
Chemical data
Formula	C15H22FN3O6
Molecular mass	359.35 g/mol
	SMILES FC=1\C(=N/C(=O)N(C=1)[C@@H]2O[C@@H]([C@@H](O)[C@H]2O)C)\NC(=O)OCCCCC ;
	InChI InChI=1S/C15H22FN3O6/c1-3-4-5-6-24-15(23)18-12-9(16)7-19(14(22)17-12)13-11(21)10(20)8(2)25-13/h7-8,10-11,13,20-21H,3-6H2,1-2H3,(H,17,18,22,23)/t8-,10-,11-,13-/m1/s1 ; Key:GAGWJHPBXLXJQN-UORFTKCHSA-N ;
(what is this?) (verify)

　　[★]

英: capecitabine
商: ゼローダ Xeloda
関: フッ化ピリミジン

[10] Includes: anaemia, lymphopenia, neutropenia and thrombocytopenia

[WikiPathways-13] The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

[AMH-1] Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.

[MSR-2] "Xeloda (capecitabine) dosing, indications, interactions, adverse effects, and more". Medscape Reference. WebMD. 25 January 2014.

[3] "www.who.int" (PDF).

[BNF-4] Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8.

[DM-5] "XELODA (capecitabine) tablet, film coated [Genentech, Inc.]". DailyMed. Genentech, Inc. December 2013. Retrieved 25 January 2014.

[EMA-6] "Capecitabine Teva : EPAR - Product Information" (PDF). European Medicines Agency. Teva Pharma B.V. 10 January 2014. Retrieved 25 January 2014.

[EMC-7] "Capecitabine 150mg - Summary of Product Characteristics (SPC)". electronic Medicines Compendium. Zentiva. 23 December 2013. Retrieved 25 January 2014.

[TGA-8] "NAME OF THE MEDICINE XELODA® Capecitabine" (PDF). TGA eBusiness Services. Roche Products Pty Limited. 5 December 2013. Retrieved 25 January 2014.

[Notes-9] Reddening, swelling, numbness and desquamation on palms and soles

[pmid23988873-11] Caudle, KE; Thorn, CF; Klein, TE; Swen, JJ; McLeod, HL; Diasio, RB; Schwab, M (December 2013). "Clinical Pharmacogenetics Implementation Consortium guidelines for dihydropyrimidine dehydrogenase genotype and fluoropyrimidine dosing.". Clinical pharmacology and therapeutics 94 (6): 640–5. doi:10.1038/clpt.2013.172. PMID 23988873.

[pmid21919607-12] Amstutz, U; Froehlich, TK; Largiadèr, CR (September 2011). "Dihydropyrimidine dehydrogenase gene as a major predictor of severe 5-fluorouracil toxicity.". Pharmacogenomics 12 (9): 1321–36. doi:10.2217/pgs.11.72. PMID 21919607.

匿名

検索

案内

案内

Xeloda