Capecitabine — Drug Monograph

Brand names: Xeloda

Drug class: Antimetabolite

Mechanism of Action

Oral prodrug enzymatically converted in three steps to 5-FU, with the final conversion step (thymidine phosphorylase) occurring preferentially within tumor tissue. This tumor-selective activation may improve the therapeutic index compared to systemic 5-FU. Same mechanism as 5-FU: TS inhibition and RNA incorporation.

FDA Indications

• Colorectal cancer — adjuvant (Duke C) and metastatic
• Metastatic breast cancer — anthracycline and taxane pre-treated
• HER2-overexpressing metastatic breast cancer in combination with lapatinib (Tykerb)

Common Side Effects

• Hand-foot syndrome (palmar-plantar erythrodysesthesia): most characteristic; redness, blistering, peeling of palms/soles
• Diarrhea (sometimes severe)
• Nausea, vomiting
• Fatigue
• Mucositis
• Myelosuppression (less than IV 5-FU)
• Hyperbilirubinemia

Clinical Pearl

Urea-based moisturizing creams applied to palms and soles starting from day 1 of treatment have strong evidence for reducing HFS severity. Grade 1 HFS (redness, discomfort without blisters) — continue at same dose. Grade 2 (blistering, limiting ADLs) — hold and reduce dose by 25%. Grade 3 (ulceration) — hold and reduce by 50%. Uridine triacetate (Vistogard) is the emergency antidote for capecitabine overdose or early-onset severe toxicity — start within 96 hours. In pNETs, capecitabine is used…

Related Therapies & Mechanisms

• 5-Fluorouracil (5-FU) (Adrucil) — Antimetabolite · CRC
• Trifluridine/Tipiracil (Lonsurf) — Antimetabolite · CRC
• Oxaliplatin (Eloxatin) — CRC
• Pembrolizumab (Keytruda) — Breast