Capecitabine

Capecitabine is prescribed to treat:

• Colorectal and breast cancer • Various related conditions in the oncology category • Associated symptoms and complications

It is an important medication that helps manage these conditions effectively.

Capecitabine (Xeloda) is an oral chemotherapy agent used for colorectal, breast, gastric, and pancreatic cancer. It is a prodrug designed to be converted to fluorouracil preferentially inside tumour tissue, which allows an oral drug to substitute for what was previously a continuous intravenous infusion.

Mechanism of Action

Capecitabine reaches its active form through three enzymatic steps. Carboxylesterase in the liver produces 5'-deoxy-5-fluorocytidine; cytidine deaminase, present in liver and tumour tissue, converts that to 5'-deoxy-5-fluorouridine; and thymidine phosphorylase performs the final conversion to fluorouracil.

The design rests on that last enzyme. Thymidine phosphorylase is expressed at considerably higher levels in many tumours than in normal tissue, so the final activation step occurs preferentially where the drug is wanted. Intratumoural fluorouracil concentrations substantially exceed plasma levels.

Fluorouracil then inhibits thymidylate synthase, blocking synthesis of thymidine and therefore DNA replication, and its metabolites are incorporated into RNA and DNA, disrupting both. Rapidly dividing cells are most affected — tumour cells, but also gastrointestinal mucosa, bone marrow, and skin, which is where the toxicity appears.

Capecitabine is taken with food, within 30 minutes of a meal, because absorption and the resulting exposure were characterised that way in trials. Taking it fasting changes exposure and is not how the dose was established.

Dosing is typically two weeks on, one week off, allowing normal tissue to recover between cycles.

DPD Deficiency

Fluorouracil is broken down by dihydropyrimidine dehydrogenase, and roughly 3 to 5 percent of people carry variants producing partial deficiency, with a much smaller number having near-complete deficiency.

In these patients the drug is not cleared normally and accumulates, producing severe and occasionally fatal toxicity — profound mucositis, diarrhoea, marrow failure, and neurotoxicity — after doses that would be routine for anyone else. Deaths have occurred after a single cycle.

Testing for DPD deficiency before starting has become standard in Europe and is increasingly recommended in the United States. Genotyping for the common variants, or measuring uracil levels, identifies most at-risk patients and allows dose reduction or an alternative agent.

This matters because severe early toxicity is otherwise interpreted as bad luck rather than as a predictable pharmacogenomic event that could have been anticipated. A patient who becomes severely unwell in the first cycle should have DPD status considered rather than simply being dose-reduced empirically. Our hematology team coordinates with oncology, and the MedlinePlus capecitabine entry covers prescribing detail.

Hand-Foot Syndrome

Palmar-plantar erythrodysesthesia is capecitabine's most characteristic toxicity and the one that most often forces dose reduction.

It begins as tingling, numbness, and redness of the palms and soles, progressing to swelling, peeling, blistering, and painful fissuring. At its worst it prevents walking and use of the hands, which is a substantial functional loss in someone otherwise well enough to be on oral therapy at home.

It is dose- and cumulative-exposure related, and it responds to dose reduction or a treatment break — usually resolving over one to two weeks. Preventive measures include emollients, avoiding heat and friction, avoiding tight footwear and repetitive hand pressure, and avoiding hot showers and washing up in hot water. Some evidence supports topical urea-based preparations.

Patients need to report it early, when it is mild and reversible, rather than pushing through until they cannot walk. This is worth stating explicitly, because patients on cancer treatment frequently minimise symptoms out of a wish not to interrupt therapy.

Monitoring and Follow-Up

Complete blood count, liver function, and kidney function are monitored each cycle. Capecitabine is renally cleared to a significant degree and requires dose reduction in moderate impairment; it is contraindicated in severe impairment.

Diarrhoea is common and can become severe, and it is the toxicity most likely to cause dangerous dehydration and kidney injury at home. Patients need a clear threshold for stopping the drug and making contact — typically an increase of four or more stools a day over baseline, or any nocturnal diarrhoea — rather than waiting for a scheduled appointment.

Mucositis, nausea, and fatigue are common. Cardiotoxicity, including coronary vasospasm and angina, occurs and warrants prompt assessment of any chest pain.

The interaction with warfarin is clinically important and frequently underestimated: capecitabine markedly potentiates it, with INR rises and serious bleeding reported, sometimes weeks after starting. INR requires much closer monitoring, and many patients are switched to an alternative anticoagulant. The American Cancer Society chemotherapy resource covers what patients should expect.

Special Populations

In older adults, toxicity is more frequent and dose reduction is often appropriate from the outset. In renal impairment, dose adjustment is required and severe impairment is a contraindication.

Capecitabine is contraindicated in pregnancy and breastfeeding, and effective contraception is required during treatment and afterwards for both men and women. In hepatic impairment due to metastases, monitoring is intensified.

Oral chemotherapy shifts responsibility to the patient in a way intravenous treatment does not — there is no nurse checking the count before each dose, no infusion visit where symptoms surface. Written instructions on what to hold for, and a clear contact route, matter more than with infused regimens.

When to Contact Your Doctor

Stop the drug and contact us for diarrhoea of four or more stools a day above your normal, any diarrhoea overnight, vomiting preventing fluid intake, mouth sores that stop you eating or drinking, or fever.

Seek emergency care for fever during treatment — in a patient on chemotherapy this is a medical emergency requiring immediate antibiotics — and for chest pain, which may indicate coronary vasospasm.

Report hand and foot redness, tingling, or soreness early, while it is still mild. Report yellowing of the skin or eyes, or reduced urine output.

To review your treatment, manage side effects, or discuss dose adjustment, contact us or schedule a visit.