Capecitabine (Xeloda)

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

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

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

Adverse Effects

Cardiovascular Adverse Effects

Cardiotoxicity

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

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

References

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