Drug/Small Molecule:
capecitabine

Available Guidelines

  1. CPIC Dosing Guideline for capecitabine and DPYD
  2. Dutch Pharmacogenetics Working Group Guideline for capecitabine and DPYD

last updated 07/30/2014

CPIC Dosing Guideline for capecitabine and DPYD

Summary

The CPIC Dosing Guidelines for fluoropyrimidines (i.e. 5-fluorouracil, capecitabine or tegafur) recommends an alternative drug for patients who are homozygous for DPYD non-functional variants - *2A (rs3918290), *13 (rs55886062), and rs67376798 A (on the positive chromosomal strand) - as these patients are typically DPD deficient. Consider a 50% reduction in starting dose for heterozygous patients (intermediate activity).

Annotation

May 2014 Update on PharmGKB

December 2013 Publication

Accepted article preview online August 2013; Advance online publication October 2013.

  • Guidelines regarding the use of pharmacogenomic tests in dosing for fluoropyrimidines have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).
  • These guidelines are applicable to:
    • at the time of this writing, there are no data available on the possible role of DPYD*2A, *13, or rs67376798 in 5-fluorouracil toxicities in pediatric patient populations; however, there is no reason to suspect that DPYD variant alleles would affect 5-fluorouracil metabolism differently in children compared to adults.
  • Excerpt from the fluoropyrimidine dosing guideline based on DPYD genotype:
    • "The strength of the dosing recommendations is based on the fact that some variants (DPYD*2A, *13, and rs67376798) clearly affect DPD activity, and DPD activity is clearly related to 5-fluorouracil clearance, and 5-fluorouracil exposure is associated with its toxic effects. Therefore, reduction of fluoropyrimidine dosage in patients with these variants may prevent severe and possibly life-threatening toxicities. However, available evidence does not clearly indicate a degree of dose reduction needed to prevent fluoropyrimidine related toxicities...[Based on literature review (see full manuscript),] our recommendation is to start with at least a 50% reduction of the starting dose followed by an increase in dose in patients experiencing no or clinically tolerable toxicity to maintain efficacy, a decrease in dose in patients who do not tolerate the starting dose to minimize toxicities or pharmacokinetic guided dose adjustments (if available). Patients who are homozygous for DPYD*2A, *13, or rs67376798 may demonstrate complete DPD deficiency and the use of 5-fluorouracil or capecitabine is not recommended in these patients."
  • Download and read:

Table 1: Recommended dosing of fluoropyrimidines by genotype/phenotype.

Adapted from Tables 1 and 2 of the 2013 guideline manuscript.

Phenotype (genotype) Examples of diplotypes Implications for phenotypic measures Dosing recommendations Classification of recommendations a
Homozygous wild-type or normal, high DPD activity (two or more functional *1 alleles) *1/*1 Normal DPD activity and "normal" risk for fluoropyrimidine toxicity Use label-recommended dosage and administration Moderate
Heterozygous or intermediate activity (~3-5% of patients), may have partial DPD deficiency, at risk for toxicity with drug exposure (one functional allele *1, plus one nonfunctional allele - *2A, *13 or rs67376798A c) *1/*2A; *1/*13; *1/ rs67376798A c) Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs Start with at least a 50% reduction in starting dose followed by titration of dose based on toxicity b or pharmacokinetic test (if available) Moderate
Homozygous variant, DPD deficiency (~0.2% of patients), at risk for toxicity with drug exposure (2 nonfunctional alleles - *2A, *13 or rs67376798A c) *2A/*2A; *13/*13; rs67376798A c / rs67376798A c Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs Select alternate drug Strong

a Rating scheme described in 2013 supplement.
b Increase the dose in patients experiencing no or clinically tolerable toxicity to maintain efficacy; decrease the dose in patients who do not tolerate the starting dose to minimize toxicities.
c Note that the rs67376798A allele refers to the allele on the positive chromosomal strand. This is important because DPYD is on the minus chromosomal strand and rs67376798 is a T/A snp. Therefore, the T allele on the gene confers the deficiency, while the complement on the positive chromosomal strand (A allele) is indicative of deficiency.


last updated 08/10/2011

Dutch Pharmacogenetics Working Group Guideline for capecitabine and DPYD

Summary

Select an alternate drug to capecitabine for DPYD poor metabolizer patients, and reduce capecitabine dose (by 50%) or select an alternate drug for DPYD intermediate metabolizers.

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for capecitabine (a fluorouracil prodrug) based on DPYD genotype [Article:21412232]. They recommend that an alternate drug be used for poor metabolizer patients, and a reduced dose or alternate drug for intermediate metabolizer patients.

Phenotype (Genotype) Therapeutic Dose Recommendation Level of Evidence Clinical Relevance
PM (2 inactive alleles, 2 decreased activity alleles, or one inactive and one decreased activity alleles) Select alterantive drug. Tegafur is not a suitable alternative because this drug is also metabolized by DPD. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
IM (1 active allele and 1 inactive or decreased activity allele) Reduce dose by 50% or select alternative drug. Tegafur is not a suitable alternative because this drug is also a substrate for DPD. Increase dose in response to toxicity and efficacy. Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpoints. Clinical effect (S): death; arrhythmia; unanticipated myelosuppression.
Allele Type Alleles
active *1, *4, *5, *6, *9A
decreased activity *9B, *10
inactive *2A, *3, *7, *8, *11, *12, *13, 496A>G, IVS10-15T>C, 1156G>T, 1845G>T
  • *See Methods or PMID: 18253145 for definition of "moderate" quality.
  • S: statistically significant difference.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for capecitabine and DPYD

This label is on the FDA Biomarker List
Actionable PGx

Summary

Variants in the DPYD gene (also known as dihydropyrimidine dehydrogenase and DPD) are associated with increased risk for adverse and potentially toxic events, and therefore Capecitabine (Xeloda) is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency (though genetic testing or screening of DPD activity is not mentioned in the drug label).

Annotation

Capecitabine is a pro-drug of 5-fluorouracil used for the treatment of various types of neoplasms including colorectal and breast neoplasms. Variants in the DPYD gene (also known as dihydropyrimidine dehydrogenase and DPD) are associated with increased risk for adverse events. See the Fluroropyrimidine Pathway and DPYD VIP for more information.

Excerpts from the capecitabine (Xeloda) drug label:

XELODA is contraindicated in patients with known dihydropyrimidine dehydrogenase (DPD) deficiency.


Rarely, unexpected, severe toxicity (eg, stomatitis, diarrhea, neutropenia and neurotoxicity) associated with 5-fluorouracil has been attributed to a deficiency of dihydropyrimidine dehydrogenase (DPD) activity. A link between decreased levels of DPD and increased, potentially fatal toxic effects of 5-fluorouracil therefore cannot be excluded.

The label also notes drug-drug interactions with warfarin and phenytoin and cautions that care should be exercised when XELODA is coadministered with CYP2C9 substrates.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Capecitabine drug label.

*Disclaimer: The contents of this page have not been endorsed by the FDA and are the sole responsibility of PharmGKB.

Full label available at DailyMed

Genes and/or phenotypes found in this label

  • Breast Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Colorectal Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Diarrhea
    • Warnings section, Adverse reactions section
    • source: PHONT
  • Neoplasms
    • Indications & usage section, Warnings section, Adverse reactions section
    • source: PHONT
  • Neutropenia
    • Warnings section, Adverse reactions section
    • source: PHONT
  • CYP2C9
    • Drug interactions section, metabolism/PK
    • source: FDA Label
  • DPYD
    • Contraindications section, Information for patients section, Pharmacokinetics section, Warnings and precautions section, toxicity, metabolism/PK
    • source: FDA Label

last updated 10/25/2013

European Medicines Agency (EMA) Label for capecitabine and DPYD

Actionable PGx

Summary

The EMA European Public Assessment Report (EPAR) highlights information regarding the contraindication of capecitabine in patients with known DPD deficiency (DYPD) due to an increased likelihood of toxicity.

Annotation

Excerpt from the capecitabine (Xeloda) EPAR:

"5-FU is further catabolised by the enzyme dihydropyrimidine dehydrogenase (DPD) to the much less toxic dihydro-5-fluorouracil (FUH2). Dihydropyrimidinase cleaves the pyrimidine ring to yield 5-fluoro-ureidopropionic acid (FUPA). Finally, beta-ureido-propionase cleaves FUPA to alpha-fluoro-beta- alanine (FBAL) which is cleared in the urine. Dihydropyrimidine dehydrogenase (DPD) activity is the rate limiting step. Deficiency of DPD may lead to increased toxicity of capecitabine (see section 4.3 and 4.4)."

This information is highlighted in the following sections:
Contraindications, Pharmacokinetic properties, package leaflet: information for the user - before you take Xeloda.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the capecitabine EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1042858 2232G>A, 4099466G>A, 4159466G>A, 48543G>A, Ala744=, RRM1:2464G>A, rs1042858
G > A
Synonymous
Ala744Ala
No VIP available CA VA
rs1045642 208920T>A, 208920T>C, 25171488A>G, 25171488A>T, 3435T>A, 3435T>C, 87138645A>G, 87138645A>T, ABCB1*6, ABCB1: 3435C>T, ABCB1: C3435T, ABCB1: c.3435C>T, ABCB1:3435C>T, Ile1145=, Ile1145Ile, MDR1 3435C>T, MDR1 C3435T, PGP C3435T, c.3435C>T, mRNA 3853C>T
A > T
A > G
Synonymous
Ile1145Ile
No VIP available No Clinical Annotations available VA
rs1047840 1765G>A, 242042301G>A, 35560080G>A, 35809G>A, Glu589Lys
G > A
Missense
Glu589Lys
No VIP available CA VA
rs1048943 1384A>C, 1384A>G, 1384A>T, 3103T>A, 3103T>C, 3103T>G, 45803542T>A, 45803542T>C, 45803542T>G, 75012985T>A, 75012985T>C, 75012985T>G, CYP1A1*2C, CYP1A1:2455A>G, CYP1A1:4889A>G, CYP1A1:Hinc II, CYP1A1:I462V, CYP1A1:m2, Ile462Leu, Ile462Phe, Ile462Val
T > G
T > C
T > A
Missense
Ile462Val
Ile462Leu
Ile462Phe
No VIP available No Clinical Annotations available VA
rs1051266 3952235T>C, 46957794T>C, 80A>G, 9592A>G, : 80A>G, His27Arg, RFC-1, SCL19A1:80G>A, SLC19A1:Arg27His, SLC19A1:G80A, mRNA 199A>G
T > C
Missense
His27Arg
No VIP available No Clinical Annotations available VA
rs1056836 10122C>C, 1294C>C, 17120090C>G, 38298203C>G, CYP1B1*3, CYP1B1: L432V, CYP1B1:4326 C>G, CYP1B1:L432V, Leu432=
G > C
Not Available
No VIP available No Clinical Annotations available VA
rs11075646 -171C>G, -850G>C, -909G>C, 20583375C>G, 66969176C>G, 803C>G
C > G
Not Available
No VIP available No Clinical Annotations available VA
rs112723255 -14+175G>A, -14+420G>A, -368G>A, -398G>A, 1393G>A, 1408G>A, 22611C>T, 50964255C>T, 549478C>T, 5614G>A, 9260G>A, Ala465Thr, Ala470Thr
G > T
G > C
5' Flanking
Ala470Thr
No VIP available No Clinical Annotations available VA
rs1128503 1236T>C, 167964T>C, 25043506A>G, 87550285A>G, ABCB1 1236C>T, ABCB1*8, ABCB1: c.1236T>C, ABCB1:1236C>T, ABCB1:1236T>C, Gly412=, Gly412Gly, mRNA 1654T>C, p.Gly412Gly
A > G
Not Available
Gly412Gly
No VIP available CA VA
rs11479 -14+194C>T, -14+439C>T, -349C>T, -379C>T, 1412C>T, 1427C>T, 22592G>A, 50964236G>A, 549459G>A, 5633C>T, 9279C>T, Ser471Leu, Ser476Leu
C > G
C > A
5' Flanking
Ser476Leu
No VIP available No Clinical Annotations available VA
rs11615 18191871A>G, 354T>C, 45923653A>G, 63434T>C, Asn118=, ERCC1:19007T>C, ERCC1:Asn118Asn
A > G
Synonymous
Asn118Asn
No VIP available No Clinical Annotations available VA
rs12022243 1906-14763G>A, 528836G>A, 67834698C>T, 97862780C>T
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs12132152 67494922G>A, 97523004G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs13181 *304T>G, 18123137T>G, 2251A>C, 23927A>C, 45854919T>G, ERCC2 Lys751Gln, ERCC2:2251A>C, ERCC2:Lys751Gln, Lys751Gln, rs13181:T>G
T > G
Missense
Lys751Gln
No VIP available No Clinical Annotations available VA
rs16430 *145-368delA, *145-368delAinsCTTTAA, *447delT, *447delTinsTTAAAG, *861delA, *861delAinsCTTTAA, 20841delT, 20841delTinsTTAAAG, 663444delT, 663444delTinsTTAAAG, 673444delT, 673444delTinsTTAAAG
T > -
T > GAAATT
3' UTR
No VIP available No Clinical Annotations available VA
rs17160359 25379662G>T, 458+6848G>T, 509+6848G>T, 746C>A, 87346819G>T
G > T
Intronic
No VIP available CA VA
rs17376848 1896T>C, 475992T>C, 67887542A>G, 97915624A>G, Phe632=, Phe632Phe
A > G
Synonymous
Phe632Phe
No VIP available No Clinical Annotations available VA
rs17431184 102056T>C, 40524715T>C, 802-400T>C, 89720251T>C
T > C
Intronic
No VIP available No Clinical Annotations available VA
rs1799793 11587G>A, 18135477C>T, 45867259C>T, 862G>A, 934G>A, Asp288Asn, Asp312Asn, XPD Asp312Asn, XPD:Asp312Asn
C > T
Missense
Asp288Asn
No VIP available No Clinical Annotations available VA
rs1800440 10186A>G, 1358A>G, 17120026T>C, 38298139T>C, Asn453Ser
T > C
Missense
Asn453Ser
No VIP available CA VA
rs1801019 124456742G>C, 12530G>C, 30951888G>C, 590G>C, 638G>C, 843G>C, Gly213Ala, OPRT: Gly213Ala
G > C
Not Available
Gly213Ala
No VIP available CA VA
rs1801131 1040A>C, 11208431T>G, 11794419T>G, 1286A>C, 1409A>C, 16685A>C, A1298C, Glu347Ala, Glu429Ala, Glu470Ala, MTHFR:1298A>C
T > G
Not Available
Glu347Ala
No VIP available CA VA
rs1801133 11210333G>A, 11796321G>A, 14783C>T, 419C>T, 665C>T, 677C>T, 788C>T, A222V, Ala140Val, Ala222Val, Ala263Val, C677T, MTHFR: c.677C>T, MTHFR:667C>T, p.A222V
G > A
Not Available
Ala140Val
No VIP available No Clinical Annotations available VA
rs1801159 1627A>G, 410221A>G, 67953313T>C, 97981395T>C, DPYD*5, DPYD:A1627G, DPYD:I543V, Ile543Val
T > C
Missense
Ile543Val
No VIP available No Clinical Annotations available VA
rs1801160 129-825C>T, 2194G>A, 620696G>A, 67742838C>T, 97770920C>T, Val732Ile
C > T
Missense
Val732Ile
No VIP available CA VA
rs1979277 1303C>T, 1420C>T, 17835470G>A, 18232096G>A, 39761C>T, Leu435Phe, Leu474Phe, SHMT1 L435F
G > A
Missense
Leu435Phe
No VIP available No Clinical Annotations available VA
rs2010963 -634C>G, -94C>G, 43678350C>G, 43738350C>G, 5398C>G, VEGF-A 405 G/C, VEGFA:405G>C, VEGFA:C405G
C > G
5' UTR
No VIP available No Clinical Annotations available VA
rs2032582 186947T>A, 186947T>G, 25193461A>C, 25193461A>T, 2677A, 2677G, 2677T, 2677T>A, 2677T>G, 3095G>T/A, 87160618A>C, 87160618A>T, 893 Ala, 893 Ser, 893 Thr, ABCB1*7, ABCB1: 2677G>T/A, ABCB1: 2677T/A>G, ABCB1: A893S, ABCB1: G2677T/A, ABCB1: c.2677G>T/A, ABCB1:2677G>A/T, ABCB1:2677G>T/A, ABCB1:A893T, Ala893Ser/Thr, MDR1, MDR1 G2677T/A, Ser893Ala, Ser893Thr, mRNA 3095G>T/A, p.Ala893Ser/Thr
A > T
A > C
Missense
Ser893Ala
Ser893Thr
No VIP available No Clinical Annotations available VA
rs2070474 -80C>G, 1-509G>C, 24891292C>G, 4281861C>G, 5042C>G
C > G
5' UTR
No VIP available No Clinical Annotations available VA
rs2072671 20915701A>C, 7595789A>C, 79A>C, CDA: c.79A>C, CDA:79A>C, K27Q, Lys27Gln, p.Lys27Gln
A > C
Missense
Lys27Gln
No VIP available No Clinical Annotations available VA
rs2236225 1958G>A, 45908845G>A, 59087G>A, 64908845G>A, Arg653Gln, MTHFD1:1958G>A, MTHFD1:Arg653Gln, R653Q
G > A
Missense
Arg653Gln
No VIP available No Clinical Annotations available VA
rs2236722 100801T>C, 115T>C, 22325552A>G, 51534995A>G, Trp39Arg
T > G
T > A
Missense
Trp39Arg
No VIP available No Clinical Annotations available VA
rs2289310 120476C>A, 30375337G>T, 4442C>A, 79570873G>T, Pro1481Gln
G > T
Missense
Pro1481Gln
No VIP available No Clinical Annotations available VA
rs2290272 412958G>A, 565G>A, 85447431G>A, SLC28A1: V189I, Val189Ile
G > A
Missense
Val189Ile
No VIP available No Clinical Annotations available VA
rs2291078 1002T>A, 1050T>A, 124458938T>A, 1255T>A, 14726T>A, 30954084T>A, Val350=
T > A
Not Available
Val350Val
No VIP available CA VA
rs2297595 226525A>G, 496A>G, 68137009T>C, 98165091T>C, DPYD:496A>G, DPYD:Met166Val, Met166Val
T > C
Missense
Met166Val
No VIP available No Clinical Annotations available VA
rs2306283 14089862A>G, 21329738A>G, 388A>G, 50611A>G, Asn130Asp, SLCO1B1*1B
A > G
Missense
Asn130Asp
No VIP available No Clinical Annotations available VA
rs25487 1196A>G, 16323944T>C, 44055726T>C, Gln399Arg, XRCC1 Arg399Gln, XRCC1:Arg399Gln
T > C
Missense
Gln399Arg
No VIP available No Clinical Annotations available VA
rs2612091 496-227G>A, 673607C>T, 683607C>T, 742-227G>A, 805-227G>A
C > T
Intronic
No VIP available No Clinical Annotations available VA
rs2669429 105463690A>G, 18737239A>G, 20588T>C, 265-58T>C
A > G
Intronic
No VIP available No Clinical Annotations available VA
rs2741171 194-3332A>G, 257-3332A>G, 63+5783A>G, 690687T>C, 700687T>C
T > C
Intronic
No VIP available CA VA
rs3215400 -33delC, 20915590delC, 7595678delC
C > -
5' UTR
No VIP available No Clinical Annotations available VA
rs3218592 111643838C>T, 15813295C>T, 8285G>A, Arg2762Gln
C > T
Missense
Arg2762Gln
No VIP available No Clinical Annotations available VA
rs34489327 *145-370delT, *145-370delTinsCTTTAA, *449delA, *449delAinsTTAAAG, *859delT, *859delTinsCTTTAA, 20843delA, 20843delAinsTTAAAG, 6-basepair 3'UTR repeat, 663446delA, 663446delAinsTTAAAG, 673446delA, 673446delAinsTTAAAG, TYMS:-TTAAAG, TYMS:1494del, TYMS:1494del TTAAAG, ttaaag
T > -
T > TTAAAG
3' UTR
No VIP available CA VA
rs34743033 28-bp tandem repeats, CCGCGCCACTTGGCCTGCCTCCGTCCCG, TSER*2, TSER*3, TYMS: 28 bp tandem repeat, TYMS: 2R, TYMS: TSER *2/*3, TYMS:TSER 28-basepair 5'UTR enhancer region repeat
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC > CCGCGCCACTTGGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCGCCGCGCCACTTCGCCTGCCTCCGTCCCCC
Not Available
No VIP available No Clinical Annotations available VA
rs3772809 124462824A>G, 1288A>G, 1336A>G, 1541A>G, 18612A>G, 30957970A>G, Ile446Val
A > G
Not Available
Ile446Val
No VIP available No Clinical Annotations available VA
rs3772810 *28A>G, 124462959A>G, 1423A>G, 1676A>G, 18747A>G, 30958105A>G
A > G
Not Available
No VIP available CA VA
rs3918290 1905+1G>A, 476002G>A, 67887532C>T, 97915614C>T, DPYD*2A, DPYD:67887533 G>A, DPYD:IVS14 + 1G>A
C > T
Donor
No VIP available No Clinical Annotations available VA
rs4149056 14091673T>C, 21331549T>C, 521T>C, 52422T>C, SLCO1B1*5, Val174Ala
T > C
Missense
Val174Ala
No VIP available No Clinical Annotations available VA
rs501415 -20+35A>G, 2109706A>G, 54318842A>G
A > G
Intronic
rs5275 *427T>C, 11502T>C, 186643058A>G, 38131700A>G, COX-2 8473T>C, PTGS2 exon10+837T>C, PTGS2: 6498T>C, PTGS2:8473T>C
A > G
3' UTR
No VIP available No Clinical Annotations available VA
rs532545 -451C>T, 20915172C>T, 7595260C>T, CDA: promoter -451C>T
C > T
5' Flanking
No VIP available CA No Variant Annotations available
rs55886062 1679T>G, 410273T>G, 67953261A>C, 97981343A>C, Ile560Ser
A > T
A > C
Missense
Ile560Asn
Ile560Ser
No VIP available No Clinical Annotations available VA
rs56038477 1236G>A, 352197G>A, 68011337C>T, 98039419C>T, Glu412=
C > T
Synonymous
Glu412Glu
No VIP available CA VA
rs602950 -92A>G, 20915531A>G, 7595619A>G
A > G
5' UTR
No VIP available CA VA
rs67376798 2846A>T, 67519865T>A, 843669A>T, 97547947T>A, Asp949Val
T > A
Missense
Asp949Val
No VIP available No Clinical Annotations available VA
rs699947 -2055A>C, -2578, -2595A>C, 3437A>C, 43676389A>C, 43736389A>C, VEGF-A -2578 C/A, VEGFA:, VEGFA:C-2578A
A > C
5' Flanking
No VIP available CA VA
rs75017182 1129-5923C>G, 346167C>G, 68017367G>C, 98045449G>C
G > C
Intronic
No VIP available No Clinical Annotations available VA
rs7548189 1906-19696G>T, 523903G>T, 67839631C>A, 97867713C>A
C > A
Intronic
No VIP available No Clinical Annotations available VA
rs76387818 67511318G>A, 97539400G>A
G > A
Not Available
No VIP available No Clinical Annotations available VA
rs8071253 -1392C>T, 117+953G>A, 41458619G>A, 63+953G>A, 76184467G>A
G > A
Intronic
No VIP available No Clinical Annotations available VA
rs8175347 233760235_233760236TA[5][6][7][8], 5-TA insertion in promoter, 7-TA insertion in promoter, 8-TA insertion in promoter, UGT1A1*28, UGT1A1*36, UGT1A1*37, microsatellite, short tandem repeat
(TA)6 > (TA)8
(TA)6 > (TA)5
(TA)6 > (TA)7
Not Available
No VIP available No Clinical Annotations available VA
rs8192924 2047G>A, 20588598G>A, 66974399G>A, 809G>A, Arg270His
G > A
Not Available
Arg270His
No VIP available No Clinical Annotations available VA
rs833061 -1498C>T, -460, -958C>T, 43677486C>T, 43737486C>T, 4534C>T, VEGF-A -460 C/T, VEGFA:C-460T, VEGFA:T-1498C
C > T
5' Flanking
No VIP available CA VA
rs9936750 55171874T>C, 8786073T>C
T > C
Not Available
No VIP available No Clinical Annotations available VA
rs9937 2223A>G, 4099457A>G, 4159457A>G, 48534A>G, RRM1:2455A>G, Thr741=, rs3177016
A > G
Synonymous
Thr741Thr
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • R340
  • capecitabine
Trade Names
  • Xeloda
Brand Mixture Names

PharmGKB Accession Id:
PA448771

Description

Capecitabine is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to fluorouracil (antimetabolite) in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.

Source: Drug Bank

Indication

For the treatment of patients with metastatic breast cancer resistant to both paclitaxel and an anthracycline-containing chemotherapy regimen. May also be used in combination with docetaxel for the treatment of metastatic breast cancer in patients who have failed to respond to, or recurred or relasped during or following anthracycline-containing chemotherapy. Capecitabine is used alone as an adjuvant therapy following the complete resection of primary tumor in patients with stage III colon cancer when monotherapy with fluroprymidine is preferred. The use or capecitabine in combination regimens for advanced gastric cancer is currently being investigated.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase, an enzyme found in higher concentrations in many tumors compared to normal tissues or plasma. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. These metabolites cause cell injury by two different mechanisms. First, FdUMP and the folate cofactor, N5-10-methylenetetrahydrofolate, bind to thymidylate synthase (TS) to form a covalently bound ternary complex. This binding inhibits the formation of thymidylate from 2'-deaxyuridylate. Thymidylate is the necessary precursor of thymidine triphosphate, which is essential for the synthesis of DNA, therefore a deficiency of this compound can inhibit cell division. Secondly, nuclear transcriptional enzymes can mistakenly incorporate FUTP in place of uridine triphosphate (UTP) during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis through the production of fraudulent RNA.

Source: Drug Bank

Pharmacology

Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of metastatic breast cancer and colon cancer. It is an orally administered systemic prodrug that has little pharmacologic activity until it is converted to fluorouracil by enzymes that are expressed in higher concentrations in many tumors. Fluorouracil it then metabolized both normal and tumor cells to 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP).

Source: Drug Bank

Food Interaction

Take 12 hours apart, within 30 minutes of the end of breakfast and dinner to reduce nausea.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Metabolized by thymidine phosphorylase to fluoruracil.

Source: Drug Bank

Protein Binding

< 60% (mainly albumin)

Source: Drug Bank

Absorption

Readily absorbed through the GI tract (~70%)

Source: Drug Bank

Half-Life

45-60 minutes for capecitabine and its metabolites.

Source: Drug Bank

Route of Elimination

Capecitabine and its metabolites are predominantly excreted in urine; 95.5% of administered capecitabine dose is recovered in urine. Fecal excretion is minimal (2.6%). The major metabolite excreted in urine is FBAL which represents 57% of the administered dose.About 3% of the administered dose is excreted in urine as unchanged drug.

Source: Drug Bank

Chemical Properties

Chemical Formula

C15H22FN3O6

Source: Drug Bank

Isomeric SMILES

CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@H]2[C@@H]([C@@H]([C@H](O2)C)O)O

Source: Drug Bank

CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H](C)[C@@H](O)[C@H]1O

Source: Drug Bank

Canonical SMILES

CCCCCOC(=O)NC1=NC(=O)N(C=C1F)[C@@H]1O[C@H]

Source: Drug Bank

Average Molecular Weight

359.3501

Source: Drug Bank

Monoisotopic Molecular Weight

359.149263656

Source: Drug Bank

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Fluoropyrimidine Pathway, Pharmacodynamics
    Model non-tissue-specific cancer cell displaying genes which may be involved in the pharmacodynamics of the fluoropyrimidines, 5-fluorouracil (5-FU), capecitabine and tegafur.
  1. Fluoropyrimidine Pathway, Pharmacokinetics
    Representation of the metabolic pathways for fluoropyrimidines.

External Pathways

Links to non-PharmGKB pathways.

PharmGKB contains no links to external pathways for this drug. To report a pathway, click here.

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Targets

Gene Description
DPYD (source: Drug Bank)
TYMS (source: Drug Bank)

Drug Interactions

Drug Description
acenocoumarol The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)
acenocoumarol Capecitabine may increase the anticoagulant effect of acenocoumarol by increasing its serum concentration. (source: Drug Bank)
anisindione Capecitabine may increase the anticoagulant effect of anisindione by increasing its serum concentration. (source: Drug Bank)
dicumarol The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)
dicumarol Capecitabine may increase the anticoagulant effect of dicumarol by increasing its serum concentration. (source: Drug Bank)
ethotoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
fosphenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
mephenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
mephenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
phenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
phenytoin Capecitabine increases the effect of hydantoin (source: Drug Bank)
warfarin The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)
warfarin Capecitabine may increase the anticoagulant effect of warfarin by increasing its serum concentration. (source: Drug Bank)
capecitabine Capecitabine increases the effect of hydantoin (source: Drug Bank)
capecitabine Capecitabine increases the effect of hydantoin (source: Drug Bank)
capecitabine Capecitabine increases the effect of hydantoin (source: Drug Bank)
capecitabine Capecitabine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of Tolbutamide, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in Tolbutamide therapeutic and adverse effects if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank)
capecitabine The strong CYP2C9 inhibitor, Capecitabine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)
capecitabine Capecitabine may increase the serum concentration of warfarin by decreasing its metabolism. Monitor for changes in prothrombin time and therapeutic effects of warfarin if capecitabine is initiated or discontinued. Subsequent cycles of capecitabine may increase this effect. (source: Drug Bank)
capecitabine Capecitabine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if capecitabine is initiated, discontinued or dose changed. (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to capecitabine: 103

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A candidate gene study of capecitabine-related toxicity in colorectal cancer identifies new toxicity variants at DPYD and a putative role for ENOSF1 rather than TYMS. Gut. 2014. Rosmarin Dan, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Genetic Markers of Toxicity From Capecitabine and Other Fluorouracil-Based Regimens: Investigation in the QUASAR2 Study, Systematic Review, and Meta-Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014. Rosmarin Dan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Identification of genetic variants associated with capecitabine-induced hand-foot syndrome through integration of patient and cell line genomic analyses. Pharmacogenetics and genomics. 2014. Wheeler Heather E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Potentially Functional SNPs (pfSNPs) as Novel Genomic Predictors of 5-FU Response in Metastatic Colorectal Cancer Patients. PloS one. 2014. Wang Jingbo, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Excision Repair Cross-Complementation group 1 (ERCC1) C118T SNP does not affect cellular response to oxaliplatin. Mutation research. 2013. van Huis-Tanja Lieke H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Polymorphism of TS 3'-UTR predicts survival of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2013. Gao J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium Guidelines for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing. Clinical pharmacology and therapeutics. 2013. Caudle Kelly E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
DPYD IVS14+1G>A and 2846A>T genotyping for the prediction of severe fluoropyrimidine-related toxicity: a meta-analysis. Pharmacogenomics. 2013. Terrazzino Salvatore, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic variants in the DPYD, TYMS, CDA and MTHFR genes are clinically significant predictors of fluoropyrimidine toxicity. British journal of cancer. 2013. Loganayagam A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Fixed-dose capecitabine is feasible: results from a pharmacokinetic and pharmacogenetic study in metastatic breast cancer. Breast cancer research and treatment. 2013. Rudek Michelle A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic analysis of adjuvant FOLFOX for Korean patients with colon cancer. Cancer chemotherapy and pharmacology. 2013. Lee Kyung-Hun, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A DPYD Variant (Y186C) in Individuals of African Ancestry Is Associated With Reduced DPD Enzyme Activity. Clinical pharmacology and therapeutics. 2013. Offer S M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule. Internal and emergency medicine. 2013. Magnani Elena, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
MTHFR polymorphisms and capecitabine-induced toxicity in patients with metastatic colorectal cancer. Pharmacogenetics and genomics. 2013. van Huis-Tanja Lieke H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and pharmacogenomics: a bridge to individualized cancer therapy. Pharmacogenomics. 2013. Weng Liming, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic variability & chemotoxicity of 5-fluorouracil & cisplatin in head & neck cancer patients: a preliminary study. The Indian journal of medical research. 2013. Dhawan Dipali, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Dihydropyrimidine Dehydrogenase Gene (DPYD) Polymorphism among Caucasian and non-Caucasian Patients with 5-FU- and Capecitabine-related Toxicity Using Full Sequencing of DPYD. Cancer genomics & proteomics. 2013. Saif Muhammad Wasif. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Evaluating predictive pharmacogenetic signatures of adverse events in colorectal cancer patients treated with fluoropyrimidines. PloS one. 2013. Jennings Barbara A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
SLCO1B1 and SLC19A1 Gene Variants and Irinotecan-Induced Rapid Response and Survival: A Prospective Multicenter Pharmacogenetics Study of Metastatic Colorectal Cancer. PloS one. 2013. Huang Liu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Contribution of the beta-ureidopropionase (UPB1) gene alterations to the development of fluoropyrimidine-related toxicity. Pharmacological reports : PR. 2012. Fidlerova Julie, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine. Journal of cancer research and clinical oncology. 2012. Dong Ningning, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Relationship between antimetabolite toxicity and pharmacogenetics in Turkish cancer patients. Asian Pacific journal of cancer prevention : APJCP. 2012. Dogan Mutlu, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy. Pharmacogenomics. 2011. Giovannetti Elisa, et al. PubMed
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SNPs and Haplotypes in DPYD and Outcome of Capecitabine-Letter. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. van Kuilenburg André B P, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Vascular endothelial growth factor polymorphisms and clinical outcome in colorectal cancer patients treated with irinotecan-based chemotherapy and bevacizumab. The pharmacogenomics journal. 2011. Koutras A K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer. Pancreas. 2011. Zeng Hongmei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Hu-Lieskovan Siwen, et al. PubMed
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Relationship between single nucleotide polymorphisms and haplotypes in DPYD and toxicity and efficacy of capecitabine in advanced colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Deenen Maarten J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Associations of various gene polymorphisms with toxicity in colorectal cancer patients receiving oral uracil and tegafur plus leucovorin: a prospective study. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 2011. Tsunoda A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A POLYMORPHISM IN THE CYTIDINE DEAMINASE PROMOTER PREDICTS SEVERE CAPECITABINE-INDUCED HAND-FOOT SYNDROME. Clinical cancer research : an official journal of the American Association for Cancer Research. 2011. Caronia Daniela, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The predictive value of genetic variations in the vascular endothelial growth factor A gene in metastatic colorectal cancer. The pharmacogenomics journal. 2011. Hansen T F, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic Tailoring of Irinotecan-based First-line Chemotherapy in Metastatic Colorectal Cancer: Results of a Pilot Study. Anticancer research. 2011. Freyer Gilles, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Associations between gene polymorphisms of thymidylate synthase with its protein expression and chemosensitivity to 5-fluorouracil in pancreatic carcinoma cells. Chinese medical journal. 2011. Zhang Qiang, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Phase II study of preoperative radiation plus concurrent daily tegafur-uracil (UFT) with leucovorin for locally advanced rectal cancer. BMC cancer. 2011. Cellier Patrice, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic contribution to drug response. Cancer journal (Sudbury, Mass.). 2011. Watson Roshawn G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
X-Ray Cross-Complementing Group 1 and Thymidylate Synthase Polymorphisms Might Predict Response to Chemoradiotherapy in Rectal Cancer Patients. International journal of radiation oncology, biology, physics. 2010. Lamas Maria J, et al. PubMed
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ABCB1 gene polymorphisms are associated with adverse reactions in fluoropyrimidine-treated colorectal cancer patients. Pharmacogenomics. 2010. Gonzalez-Haba Eva, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Value of gene polymorphisms as markers of 5-FU therapy response in stage III colon carcinoma: a pilot study. Cancer chemotherapy and pharmacology. 2010. Fariña-Sarasqueta Arantza, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thymidylate synthase germline polymorphisms in rectal cancer patients treated with neoadjuvant chemoradiotherapy based on 5-fluorouracil. Journal of cancer research and clinical oncology. 2010. Páez David, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Distribution of TYMS, MTHFR, p53 and MDR1 gene polymorphisms in patients with breast cancer treated with neoadjuvant chemotherapy. Cancer epidemiology. 2010. Henríquez-Hernández Luis Alberto, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Thymidylate Synthase Gene Polymorphism Affects the Response to Preoperative 5-Fluorouracil Chemoradiation Therapy in Patients With Rectal Cancer. International journal of radiation oncology, biology, physics. 2010. Hur Hyuk, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: fluoropyrimidine pathways. Pharmacogenetics and genomics. 2010. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer. The pharmacogenomics journal. 2010. Ho-Pun-Cheung A, et al. PubMed
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Investigation of IVS14 + 1G > A polymorphism of DPYD gene in a group of Bosnian patients treated with 5-Fluorouracil and capecitabine. Bosnian journal of basic medical sciences / Udru¿enje basi¿nih mediciniskih znanosti = Association of Basic Medical Sciences. 2010. Ceri¿ Timur, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rationally designed pharmacogenomic treatment using concurrent capecitabine and radiotherapy for glioblastoma; gene expression profiles associated with outcome. Clinical cancer research : an official journal of the American Association for Cancer Research. 2010. Grunda Jessica M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacogenetic assessment of toxicity and outcome in patients with metastatic colorectal cancer treated with LV5FU2, FOLFOX, and FOLFIRI: FFCD 2000-05. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2010. Boige Valérie, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Chemotherapeutic drug susceptibility associated SNPs are enriched in expression quantitative trait loci. Proceedings of the National Academy of Sciences of the United States of America. 2010. Gamazon Eric R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Oxaliplatin, irinotecan and capecitabine as first-line therapy in metastatic colorectal cancer (mCRC): a dose-finding study and pharmacogenomic analysis. British journal of cancer. 2010. Zarate R, et al. PubMed
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Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients. BMC cancer. 2010. Savva-Bordalo Joana, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genetic polymorphisms associated with 5-Fluorouracil-induced neurotoxicity. Chemotherapy. 2010. Kim Suk-Ran, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Variants in the dihydropyrimidine dehydrogenase, methylenetetrahydrofolate reductase and thymidylate synthase genes predict early toxicity of 5-fluorouracil in colorectal cancer patients. The Journal of international medical research. 2010. Kristensen M H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evolving novel anti-HER2 strategies. The lancet oncology. 2009. Jones Kellie L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Association of molecular markers with toxicity outcomes in a randomized trial of chemotherapy for advanced colorectal cancer: the FOCUS trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2009. Braun Michael S, et al. PubMed
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Prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) 8473T>C polymorphism associated with prognosis for patients with colorectal cancer treated with capecitabine and oxaliplatin. Cancer chemotherapy and pharmacology. 2009. Kim Jong Gwang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Toxicity and efficacy of 5-fluorouracil and capecitabine in a patient with TYMS gene polymorphism: A challenge or a dilemma?. Clinical colorectal cancer. 2009. Shahrokni Armin, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Dihydropyrimidine dehydrogenase gene variation and severe 5-fluorouracil toxicity: a haplotype assessment. Pharmacogenomics. 2009. Amstutz Ursula, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics and biomarkers in colorectal cancer. The pharmacogenomics journal. 2009. Strimpakos A S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer. British journal of cancer. 2009. Gusella M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Early severe toxicities after capecitabine intake: possible implication of a cytidine deaminase extensive metabolizer profile. Cancer chemotherapy and pharmacology. 2009. Mercier Cedric, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. European journal of cancer (Oxford, England : 1990). 2009. De Mattia Elena, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A dynamic model of hand-and-foot syndrome in patients receiving capecitabine. Clinical pharmacology and therapeutics. 2009. Hénin E, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Influence of dihydropyrimidine dehydrogenase gene (DPYD) coding sequence variants on the development of fluoropyrimidine-related toxicity in patients with high-grade toxicity and patients with excellent tolerance of fluoropyrimidine-based chemotherapy. Neoplasma. 2009. Kleibl Z, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
The influence of fluorouracil outcome parameters on tolerance and efficacy in patients with advanced colorectal cancer. The pharmacogenomics journal. 2008. Capitain O, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
UGT1A1*28 genotype and irinotecan dosage in patients with metastatic colorectal cancer: a Dutch Colorectal Cancer Group study. British journal of cancer. 2008. Kweekel D M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Capecitabine: an overview of the side effects and their management. Anti-cancer drugs. 2008. Saif Muhammad Wasif, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PK/PD model of indisulam and capecitabine: interaction causes excessive myelosuppression. Clinical pharmacology and therapeutics. 2008. Zandvliet A S, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacokinetics of 5-fluorouracil in patients heterozygous for the IVS14+1G > A mutation in the dihydropyrimidine dehydrogenase gene. Nucleosides, nucleotides & nucleic acids. 2008. van Kuilenburg A B P, et al. PubMed
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A carboxylesterase 2 gene polymorphism as predictor of capecitabine on response and time to progression. Current drug metabolism. 2008. Ribelles N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Role of genetic and nongenetic factors for fluorouracil treatment-related severe toxicity: a prospective clinical trial by the German 5-FU Toxicity Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2008. Schwab Matthias, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphisms and toxicity to capecitabine in advanced colorectal cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2008. Sharma Rohini, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Capecitabine and oxaliplatin for advanced esophagogastric cancer. The New England journal of medicine. 2008. Cunningham David, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
5-Fluorouracil toxicity-attributable IVS14 + 1G > A mutation of the dihydropyrimidine dehydrogenase gene in Polish colorectal cancer patients. Pharmacological reports : PR. 2008. Sulzyc-Bielicka Violetta, et al. PubMed
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Strong association of a common dihydropyrimidine dehydrogenase gene polymorphism with fluoropyrimidine-related toxicity in cancer patients. PloS one. 2008. Gross Eva, et al. PubMed
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DPYD*2A mutation: the most common mutation associated with DPD deficiency. Cancer chemotherapy and pharmacology. 2007. Saif M W, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Dihydropyrimidine dehydrogenase activity and the IVS14+1G>A mutation in patients developing 5FU-related toxicity. British journal of clinical pharmacology. 2007. Magné Nicolas, et al. PubMed
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5-Fluorouracil-related severe toxicity: a comparison of different methods for the pretherapeutic detection of dihydropyrimidine dehydrogenase deficiency. Cancer letters. 2007. Boisdron-Celle M, et al. PubMed
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Polymorphisms in the thymidylate synthase and dihydropyrimidine dehydrogenase genes predict response and toxicity to capecitabine-raltitrexed in colorectal cancer. Oncology reports. 2007. Salgado Josefa, et al. PubMed
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Clinical relevance of different dihydropyrimidine dehydrogenase gene single nucleotide polymorphisms on 5-fluorouracil tolerance. Molecular cancer therapeutics. 2006. Morel Alain, et al. PubMed
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Pharmacogenetics of capecitabine in advanced breast cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Largillier Rémy, et al. PubMed
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Orotate phosphoribosyltransferase gene polymorphism predicts toxicity in patients treated with bolus 5-fluorouracil regimen. Clinical cancer research : an official journal of the American Association for Cancer Research. 2006. Ichikawa Wataru, et al. PubMed
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Polymorphic tandem repeat sequences of the thymidylate synthase gene correlates with cellular-based sensitivity to fluoropyrimidine antitumor agents. Cancer chemotherapy and pharmacology. 2005. Yawata Ayako, et al. PubMed
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Pharmacogenetics of extraordinary responses to 5-FU/cisplatin chemotherapy in advanced gastric cancer -- report of 2 cases. Onkologie. 2005. Wolschke Christine, et al. PubMed
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Relationships between promoter polymorphisms in the thymidylate synthase gene and mRNA levels in colorectal cancers. European journal of cancer (Oxford, England : 1990). 2005. Morganti Maria, et al. PubMed
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Analysis of the DPYD gene implicated in 5-fluorouracil catabolism in a cohort of Caucasian individuals. Clinical cancer research : an official journal of the American Association for Cancer Research. 2005. Seck Katharina, et al. PubMed
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Correlations between antitumor activities of fluoropyrimidines and DPD activity in lung tumor xenografts. Oncology reports. 2005. Takechi Teiji, et al. PubMed
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Dihydropyrimidine dehydrogenase deficiency presenting at birth. Journal of inherited metabolic disease. 2005. Al-Sanna'a N A, et al. PubMed
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Mutations in exon 14 of dihydropyrimidine dehydrogenase and 5-Fluorouracil toxicity in Portuguese colorectal cancer patients. Genetics in medicine : official journal of the American College of Medical Genetics. 2004. Salgueiro Natália, et al. PubMed
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Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effects. Human mutation. 2003. Gross Eva, et al. PubMed
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Dihydropyrimidinase deficiency and severe 5-fluorouracil toxicity. Clinical cancer research : an official journal of the American Association for Cancer Research. 2003. van Kuilenburg André B P, et al. PubMed
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Identification and functional analysis of single nucleotide polymorphism in the tandem repeat sequence of thymidylate synthase gene. Cancer research. 2003. Kawakami Kazuyuki, et al. PubMed
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Identification of a novel human uridine phosphorylase. Biochemical and biophysical research communications. 2003. Johansson Magnus. PubMed
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5-fluorouracil: mechanisms of action and clinical strategies. Nature reviews. Cancer. 2003. Longley Daniel B, et al. PubMed
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Uridine phosphorylase (-/-) murine embryonic stem cells clarify the key role of this enzyme in the regulation of the pyrimidine salvage pathway and in the activation of fluoropyrimidines. Cancer research. 2002. Cao Deliang, et al. PubMed
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Prevalence of a common point mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5'-splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)- related toxicity compared with controls. Clinical cancer research : an official journal of the American Association for Cancer Research. 2001. Raida M, et al. PubMed
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Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. The pharmacogenomics journal. 2001. Pullarkat S T, et al. PubMed
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Known variant DPYD alleles do not explain DPD deficiency in cancer patients. Pharmacogenetics. 2000. Collie-Duguid E S, et al. PubMed
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Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 2000. van Triest B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Genotype and phenotype in patients with dihydropyrimidine dehydrogenase deficiency. Human genetics. 1999. Van Kuilenburg A B, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphic tandem repeats in the thymidylate synthase gene is associated with its protein expression in human gastrointestinal cancers. Anticancer research. 1999. Kawakami K, et al. PubMed
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Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. European journal of cancer (Oxford, England : 1990). 1998. Miwa M, et al. PubMed
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Dihydropyrimidine dehydrogenase (DPD) deficiency: identification and expression of missense mutations C29R, R886H and R235W. Human genetics. 1997. Vreken P, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0004-1100-20
DrugBank:
DB01101
ChEBI:
31348
KEGG Compound:
C12650
KEGG Drug:
D01223
PubChem Compound:
60953
PubChem Substance:
197173
46508686
Drugs Product Database (DPD):
2238454
ChemSpider:
54916
Therapeutic Targets Database:
DAP000761
FDA Drug Label at DailyMed:
a1de8bba-3b1d-4c9d-ab8a-32d2c05e67c8

Clinical Trials

These are trials that mention capecitabine and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.