Capecitabine

Capecitabine is an oral chemotherapeutic agent that is a prodrug of the fluoropyrimidine 5-fluorouracil (5-FU). It is activated in vivo to 5-FU, with most conversion occurring in tumor tissue due to higher thymidine phosphorylase activity, an approach intended to improve tumor selectivity and reduce systemic toxicity.

Medical uses: Capecitabine is approved for metastatic colorectal cancer, often as part of the XELOX regimen with oxaliplatin, and as adjuvant therapy for stage III colon cancer. It is also used to treat metastatic breast cancer, either as monotherapy or in combination with agents such as paclitaxel or trastuzumab, in patients whose disease has progressed after standard therapy.

Mechanism and pharmacokinetics: Capecitabine undergoes enzymatic conversion in three steps to 5-FU, with final activation in tumor tissue by thymidine phosphorylase. 5-FU then inhibits thymidylate synthase and is incorporated into RNA and DNA, disrupting nucleic acid synthesis and function. The oral route provides systemic exposure largely as a prodrug of 5-FU, with tissue-selective activation contributing to its activity and toxicity profile.

Administration and dosing: Capecitabine is taken orally in divided doses twice daily on schedules that vary by indication, commonly 14 days on followed by 7 days off in a 21-day cycle. Dose adjustments are recommended for renal or hepatic impairment and in the context of drug interactions. For renal impairment, a reduced dose is used if creatinine clearance is 30-50 mL/min; use is generally avoided if CrCl is below 30 mL/min.

Adverse effects and safety: Common toxicities include hand-foot syndrome, diarrhea, nausea, vomiting, mucositis, and fatigue. Myelosuppression is less pronounced than with IV 5-FU. Severe hepatotoxicity and QT prolongation are possible. Capecitabine can interact with anticoagulants such as warfarin, increasing bleeding risk. It is contraindicated in severe DPD deficiency and in patients with severe renal impairment.

History and regulatory status: Capecitabine is marketed under the brand name Xeloda in many regions and has been approved since the late 1990s for colorectal cancer and breast cancer.