PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
capecitabine

2D structure

Overview

Generic Names: R340; capecitabine
Trade Names: Xeloda
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 5-fluorouracil 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. (source: Drug Bank)

ATC Therapeutic Category

  • L01BC:Pyrimidine analogues

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Capecitabine is a prodrug that is selectively tumour-activated to its cytotoxic moiety, fluorouracil, by thymidine phosphorylase. Fluorouracil is further metabolized to two active metabolites, 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP), within normal and tumour cells. FdUMP inhibits DNA synthesis by reducing normal thymidine production, while FUTP inhibits RNA and protein synthesis by competing with uridine triphosphate.3 The active moiety of capecitabine, fluorouracil, is cell cycle phase-specific (Sphase). Both normal and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). 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, so that a deficiency of this compound can inhibit cell division. Second 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. (source: Drug Bank)

Pharmacology

Capecitabine is a fluoropyrimidine carbamate with antineoplastic activity indicated for the treatment of patients with metastatic breast cancer. It is an orally administered systemic prodrug of 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5-fluorouracil. (source: Drug Bank)

Food Interactions

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% (source: Drug Bank)

Isomeric SMILES Code:

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

Curated Annotations (Curated Annotation)

  1. rs2297595 at chr1:97937679 in DPYD
    The DPYD:496A>G variant was associated with toxicity of fluoropyrimidine-based chemotherapy in patients with gastroesophageal and breast cancer, but did not reach significance in patients with colorectal malignancies.
    Variant Name:
    DPYD:496A>G, DPYD:Met166Val
    Related Drugs:
    capecitabine, fluorouracil
    Evidence:
    PMID:19104657
  2. rs5275 at chr1:184909681 in PTGS2
    Risk or phenotype-associated allele: T. Phenotype: Homozygous TT genotype was associated with better PFS and overall survival in patients with advanced colorectal cancer treated with XELOX chemotherapy. Study size: 76. Study population/ethnicity: Colorectal Neoplasms; Korea; Asian. Significance metric(s): HR = 0.47, p = 0.046 (PFS); HR = 0.16, p = 0.013 (OS) Type of association: CO.
    Variant Name:
    PTGS2:8473T>C, COX-2 8473T>C
    Related Drugs:
    capecitabine, oxaliplatin
    Related Diseases:
    Colorectal Neoplasms
    Evidence:
    PMID:19219602
  3. rs699947 at chr6:43844367 in VEGFA
    Risk or phenotype-associated allele: CA. Phenotype: Response was observed in 21% of the patients with the -2578 CA genotype compared with 59% of the patients with CC+AA. This genotype was also associated with poor progression free survival (PFS). Study size: 72. Study population/ethnicity: Patients with metastatic colorectal neoplasms; Denmark. Significance metric(s): p = 0.002 (response); HR = 1.74, CI 1.04-2.92, p = 0.02 (PFS) Type of association: PD; CO
    Variant Name:
    VEGFA:(-2578)C>A; VEGF-A -2578 C/A
    Related Drugs:
    capecitabine, oxaliplatin
    Related Diseases:
    Colorectal Neoplasms
    Evidence:
    PMID:20125120
  4. rs833061 at chr6:43845464 in VEGFA
    Risk or phenotype-associated allele: CT. Phenotype: Response was observed in 26% of the patients with the -460 CT genotype compared with 57% with CC+TT. Study size: 72. Study population/ethnicity: Patients with metastatic colorectal neoplasms; Denmark. Significance metric(s): p = 0.01. Type of association: PD
    Variant Name:
    VEGFA:(-460)C>T; VEGF-A -460 C/T
    Related Drugs:
    capecitabine, oxaliplatin
    Related Diseases:
    Colorectal Neoplasms
    Evidence:
    PMID:20125120
  5. rs2010963 at chr6:43846328 in VEGFA
    Risk or phenotype-associated allele: GC. Phenotype: Response was observed in 27% of the patients with the +405 GC genotype compared with 54% with GG+CC. This genotype was also associated with poor progression free survival (PFS). Study size: 72. Study population/ethnicity: Patients with metastatic colorectal neoplasms; Denmark. Significance metric(s): p = 0.02 (response); HR = 1.65, CI 0.98-2.77, p = 0.04. Type of association: PD; CO
    Variant Name:
    VEGFA:405G>C; VEGF-A 405 G/C
    Related Drugs:
    capecitabine, oxaliplatin
    Related Diseases:
    Colorectal Neoplasms
    Evidence:
    PMID:20125120
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
APEX2
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CDA
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CES1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CES2
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  • PD
  • PK
  •   
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
DCTD
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
DPYD
  • CO
  • PD
  • PK
  • FA
  • GN
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
ERCC1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
ERCC2
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
ERCC6
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
FRAP1
  • CO
  •   
  •   
  • FA
  •   
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
GSTA1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
GSTM1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
GSTP1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
GSTT1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
MTHFR
  • CO
  • PD
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Has annotations
PTGS2
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
RAD54B
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
RRM1
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
RRM2
  • CO
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
SLC29A1
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
TK1
  • CO
  •   
  • PK
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
TYMP
  •   
  •   
  • PK
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
TYMS
  • CO
  • PD
  •   
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
UGT1A1
  • CO
  •   
  •   
  •   
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
UPB1
  •   
  •   
  • PK
  • FA
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
UPP1
  •   
  •   
  • PK
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
UPP2
  •   
  •   
  • PK
  • FA
  • GN
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
VEGFA
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
Phenotype data available No genotype data Literature annotations available Not annotated
XRCC1
  • CO
  •   
  •   
  •   
  • GN
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

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

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
lapatinib
  • CO
  •   
  •   
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenytoin
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
warfarin
  •   
  •   
  • PK
  •   
  •   
Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
acenocoumarol Uncurated Annotation The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)
dicumarol Uncurated Annotation The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)
mephenytoin Uncurated Annotation Capecitabine increases the effect of hydantoin (source: Drug Bank)
phenytoin Uncurated Annotation Capecitabine increases the effect of hydantoin (source: Drug Bank)
warfarin Uncurated Annotation The antineoplastic agent increases the anticoagulant effect (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Breast Neoplasms
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Colorectal Neoplasms
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Diarrhea
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Esophageal Neoplasms
  • CO
  • PD
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Glioblastoma
  • CO
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
Neoplasms
  • CO
  • PD
  • PK
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Neutropenia
  • CO
  •   
  •   
  •   
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01101
KEGG Compound ID:
C12650
KEGG Drug ID:
D01223
PubChem Compound ID:
60953
PubChem Substance ID:
197173

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
Add New Alternate Name
Add New ATC Term
Add Cross Reference
Add a metabolite
Add a text annotation
Add a drug target
hint: enter a gene
    Add a drug interaction
    hint: enter a drug
    PharmGKB® is a registered trademark of HHS and is financially supported by NIH/NIGMS. It is managed at Stanford University (GM61374).
    ©2001-2010 PharmGKB.