A 38-year-old woman with metastatic breast cancer (HER2-negative, hormone receptor-positive) is being treated with docetaxel. Due to cumulative toxicity, the oncologist switches to a single-agent antimetabolite. Which drug is the preferred choice for maintenance therapy in this setting?

Explanation

## Capecitabine in Metastatic Breast Cancer **Key Point:** Capecitabine is an oral fluoropyrimidine prodrug and the preferred single-agent antimetabolite for maintenance or palliative therapy in metastatic breast cancer, particularly after taxane-based chemotherapy. ### Mechanism and Pharmacology 1. **Prodrug activation:** Capecitabine → 5'-DFCR → 5'-DFUR → 5-FU (via thymidine phosphorylase, enriched in tumour tissue) 2. **Selective activation:** Tumour tissue has higher thymidine phosphorylase activity, allowing preferential conversion to active 5-FU 3. **Oral bioavailability:** Well-absorbed from GI tract; allows convenient outpatient dosing **High-Yield:** Capecitabine is oral 5-FU prodrug with tumour-selective activation. It is standard for metastatic breast cancer maintenance, either as monotherapy or in combination (e.g., with trastuzumab in HER2+ disease). ### Clinical Use in Metastatic Breast Cancer - **Monotherapy:** For patients who have progressed on or are intolerant to taxanes/anthracyclines - **Combination:** With trastuzumab (HER2+), with hormonal agents, or with other chemotherapy - **Maintenance:** Preferred due to oral route, tolerability, and activity **Clinical Pearl:** Hand-foot syndrome (palmar-plantar erythrodysesthesia) is the dose-limiting toxicity of capecitabine; it is reversible with dose reduction or interruption. ### Comparison with Other Antimetabolites | Drug | Class | Primary Use | Why Not Here | | --- | --- | --- | --- | | **Capecitabine** | Fluoropyrimidine | Metastatic breast cancer, colorectal | — | | **Pemetrexed** | Multitargeted antifolate | Mesothelioma, non-squamous NSCLC | Not indicated in breast cancer | | **Cladribine** | Purine analogue | Hairy cell leukaemia, CLL | Haematologic malignancy agent; not breast cancer | | **Azacitidine** | Hypomethylating agent | MDS, AML | Epigenetic agent; not standard in solid tumours | **Mnemonic:** **CAPE** = **C**apecitabine for **A**dvanced **P**rognosis **E**ncountered (metastatic breast cancer maintenance). [cite:KD Tripathi 8e Ch 62; Harrison 21e Ch 105]