Indications

• Breast Cancer (see Breast Cancer, Breast Cancer)
  • Metastatic Breast Cancer
• Colorectal Cancer (see Colorectal Cancer, Colorectal Cancer)
  • First-Line Therapy in Metastatic Colorectal Cancer When Fluoropyrimidine Alone is the Preferred Therapy
  • Adjuvant Therapy of Duke’s C Colorectal Cancer After Complete Resection of Primary Tumor When Fluoropyrimidine Alone is the Preferred Therapy
• Esophageal Cancer (see Esophageal Cancer, Esophageal Cancer): off-label use
• Hepatobiliary Cancer: off-label use
• Malignancy of Unknown Primary: off-label use
• Neuroendocrine Pancreatic Iselt Cell Tumors: off-label use
• Ovarian Cancer/Fallopian Tube Cancer/Peritoneal Cancer (see Ovarian Cancer, Ovarian Cancer): off-label use
• Pancreatic Cancer (see Pancreatic Cancer, Pancreatic Cancer): off-label use

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Pharmacology

• Prodrug of Fluorouracil: hydrolyzed in the liver to form fluorouracil, which is the active compound (see 5-Fluorouracil, 5-Fluorouracil)
  • 5-Fluorouracil is a Fluorinated Pyrimidine Antimetabolite Which Inhibits Thymidylate Synthetase: blocks the methylation of deoxyuridylic acid to thymidylic acid, interfering with DNA synthesis (and to a lesser extent, RNA synthesis)
    • 5-Fluorouracil appears to be phase-specific for the G1 and S phases of the cell cycle

Metabolism

• Hepatic: to inactive metabolites 5′-deoxy-5-fluorocytidine and 5′-deoxy-5-fluorouridine
• Tissue: enzymatically metabolized to fluorouracil –> this is then metabolized to the active metabolites, 5-fluoxyuridine monophosphate (F-UMP) and 5-5-fluoro-2′-deoxyuridine-5′-O-monophosphate (F-dUMP)
• Elimination Half-Life: 0.75 hr

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Administration

• PO:

Dose Adjustment

• Hepatic
  • Mild-Moderate Impairment: no dose adjustment necessary
  • Severe Impairment: has not been studied
• Renal
  • CrCl >51 mL/min: no dose adjustment necessary
  • CrCl 30-50 mL/min: administer 75% of usual dose
  • CrCl <30 mL/min: use is contraindicated

Drug Interactions

• Coumadin (see Coumadin, Coumadin): capecitabine may increased effects of coumadin
  • Effects may continue for up to 1 mo after capecitabine discontinuation
  • May occur in patients with/without liver metastases

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Adverse Effects

Cardiovascular Adverse Effects

Cardiotoxicity

• General Comments: increased risk in patients with coronary artery disease
• Cardiac Arrest (see Cardiac Arrest, Cardiac Arrest)
• Cardiomyopathy (see Congestive Heart Failure, Congestive Heart Failure)
• Electrocardiographic (EKG) Changes (see Electrocardiogram, Electrocardiogram)
• Myocardial Ischemia/Infarction (MI) (see Coronary Artery Disease, Coronary Artery Disease)

Dermatologic Adverse Effects

Chemotherapy-Induced Acral Erythema (Hand-Foot Syndrome, Palmar-Plantar Erythrodysesthesia) (see Chemotherapy-Induced Acral Erythema, Chemotherapy-Induced Acral Erythema)

• Epidemiology
  • Incidence: 54-60% of cases (however, grade at least 3 occurs in only 11-17% of cases)
  • Median Onset: 79 days
• Clinical
  • Desquamation/Blistering
  • Dysesthesia/Parasthesias
  • Erythema
  • Numbness
  • Painless/Painful Edema
  • Severe Pain

Dermatitis

• Epidemiology: occurs in 27-37% of cases

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (see Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis)

• Epidemiology: fatal cases have been reported

Gastrointestinal Adverse Effects

Diarrhea (see Diarrhea, Diarrhea)

• Clinical: may be severe

Hepatoxicity (see Drug-Induced Hepatotoxicity, Drug-Induced Hepatotoxicity)

• Epidemiology: may occur
• Clinical
  • Elevated Alkaline Phosphatase
  • Hyperbilirubinemia
  • Transaminitis

Ileitis (see Gastroenteritis, Gastroenteritis)

• Epidemiology: has been reported

Nausea/Vomiting (see Nausea and Vomiting, Nausea and Vomiting)

• Epidemiology: occurs in 34-43% of cases

Necrotizing Enterocolitis/Typhlitis (see Typhlitis, Typhlitis)

• Epidemiology: has been reported

Hematologic Adverse Effects

Myelosuppression

• General Comments: increased risk with combination chemotherapy
• Anemia (see Anemia, Anemia)
• Leukopenia/Neutropenia (see Leukopenia, Leukopenia)
• Thrombocytopenia (see Thrombocytopenia, Thrombocytopenia)

Rheumatologic Adverse Effects

Peripheral Edema (see Peripheral Edema, Peripheral Edema)

• Epidemiology: occurs in <15% of cases

Other Adverse Effects

Fever (see Fever, Fever)

• Epidemiology: occurs in 7-18% of cases

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References

• Ileitis secondary to oral capecitabine treatment? Case Rep Med. 2012;2012:154981 [MEDLINE]