CAPOX (XELOX)

Oxaliplatin 130 mg/m² every 21 days with oral capecitabine on days 1–14 for adjuvant and metastatic colorectal cancer

For clinicians and students · Regimen tutorial · Colorectal cancer · 7 min read · last reviewed September 30, 2026

Overview

CAPOX (also called XELOX, after the capecitabine brand name) replaces infusional fluorouracil with capecitabine. Capecitabine is an oral prodrug converted to fluorouracil in three enzymatic steps. The last step, via thymidine phosphorylase, is relatively concentrated in tumour tissue. Oxaliplatin is given as a larger dose every 3 weeks instead of every 2. The result is fewer clinic visits and no infusion pump or central line, at the price of more hand-foot syndrome and the need for a patient who can manage an oral chemotherapy schedule reliably.

Indications

BC Cancer eligibility requires ECOG ≤ 2 and adequate marrow, renal and liver function. Exclusions: creatinine clearance < 30 mL/min (Cockcroft–Gault), severe pre-existing peripheral neuropathy, and congenital long QT syndrome.

Regimen

Source: BC Cancer GIAJCAPOX / GICAPOX; eviQ ID 4019 gives the same doses.

Cycle length: 21 days.

Number of cycles

• Adjuvant, low-risk stage III (T1–3 N1): 4 cycles (3 months).
• Adjuvant, high-risk stage III (any T4 and/or N2): 8 cycles (6 months).
• eviQ 4019 lists 8 cycles as the default schedule. Its notes state that for lower-risk patients, shorter CAPOX (3 months) was equivalent to 6 months with less neurotoxicity.
• Metastatic: repeat every 21 days until progression or unacceptable toxicity.

Variants. Some metastatic protocols and trials (including the original NO16966 design) use the same 130 mg/m² / 1000 mg/m² BID schedule. Many clinicians start older or frail patients at reduced capecitabine doses. Any lower start should follow a documented local protocol, not ad hoc rounding.

Premedication and supportive care

• Antiemetics. Moderately emetogenic on day 1 (BC Cancer SCNAUSEA; eviQ "MODERATE"). Use a 5-HT3 antagonist plus dexamethasone, with or without an NK1 antagonist per local guidance. The oral capecitabine days are usually of low emetic risk.
• Oxaliplatin hypersensitivity premedication (after a grade 1–2 reaction), per BC Cancer:
• dexamethasone 20 mg IV at 45 min, then diphenhydramine 50 mg IV plus famotidine 20 mg IV at 30 min before oxaliplatin.
• Cold avoidance for 3–5 days after each oxaliplatin dose. No ice chips. Because the single oxaliplatin dose is larger, acute cold dysesthesia is often more noticeable with CAPOX than with FOLFOX.
• Capecitabine teaching.
• Take twice daily about 12 hours apart, within 30 minutes after a meal, swallowed whole.
• Do not make up missed doses.
• Keep loperamide at home.
• BC Cancer suggests considering weekly nursing assessment during the first two cycles and whenever the capecitabine dose is increased.
• Hand-foot syndrome. Use emollients and avoid friction, heat and tight footwear. Dose interruption is the main tool.
• Growth factor. Not routinely required. Febrile neutropenia risk is low with this regimen.

Key toxicities

Oxaliplatin

• Acute cold-induced dysesthesia, including pharyngolaryngeal dysesthesia (normal SpO₂, no bronchospasm; see the FOLFOX tutorial for the BC Cancer comparison table).
• Cumulative sensory neuropathy. This is dose- and duration-dependent, and is the main reason IDEA mattered clinically.
• Hypersensitivity (more likely after several cycles), QT prolongation, and rare pulmonary fibrosis, veno-occlusive disease and hemolytic uremic syndrome.

Capecitabine

• Hand-foot syndrome (palmar-plantar erythrodysesthesia). This is more frequent than with infusional 5-FU. It progresses from tingling and erythema, to painful swelling or blistering that limits function, to desquamation.
• Diarrhea can escalate quickly. Dehydration and prerenal kidney injury then raise capecitabine exposure further.
• Stomatitis, neutropenia (usually modest), and hyperbilirubinemia.
• DPD deficiency. Severe early toxicity (mucositis, diarrhea, neutropenia) in cycle 1 should prompt immediate cessation and DPD evaluation. BC Cancer mandates baseline DPYD genotyping and dosing by DPYD Activity Score:
• score 2.0 → no reduction;
• 1.0–1.5 → 50% dose reduction, titrated;
• 0.5 → not recommended (if unavoidable, ≥ 75% reduction plus early therapeutic drug monitoring);
• 0 → do not use.
• Testing policy varies by country and institution. The eviQ protocols note that testing is available in Australia but was not reimbursed at the time of writing.
• Cardiotoxicity. Chest pain from coronary vasospasm or arrhythmia: stop the drug and arrange urgent cardiac assessment. Rechallenge is generally not recommended (BC Cancer).
• Warfarin interaction. Capecitabine markedly raises the INR, and the effect can persist after stopping. Check the INR weekly until stable.

Monitoring

Per BC Cancer GIAJCAPOX:

• Baseline:
• CBC and differential, creatinine, ALT, alkaline phosphatase, total bilirubin, albumin, sodium, potassium.
• DPYD test.
• If clinically indicated: CEA, CA 19-9, GGT, ECG.
• Before each cycle: CBC and differential, creatinine (recalculate CrCl), total bilirubin, ALT. Grade neuropathy, hand-foot syndrome, diarrhea and stomatitis.
• Warfarin: INR weekly until the dose is stable, then before each cycle.
• Mid-cycle phone check or nursing visit in cycles 1–2. Most severe capecitabine toxicity appears in the second week of the first cycle.

Dose-modification principles

BC Cancer GIAJCAPOX uses separate dose-level ladders for neurologic and non-neurologic toxicity:

If both ladders apply, give the lower oxaliplatin dose.

• Day-1 thresholds. Hold if ANC < 1.2 × 10⁹/L or platelets < 75 × 10⁹/L. Recheck weekly, up to 2 times. Discontinue if not recovered within 2 weeks. Grade 3 cytopenias reduce both drugs one level; grade 4 reduces both drugs two levels.
• Mid-cycle rule. For grade 2, 3 or 4 non-hematologic toxicity, interrupt capecitabine immediately and resume only once the toxicity is grade ≤ 1. The skipped days are lost, not added on.
• Diarrhea, stomatitis, hand-foot syndrome. Hold for grade ≥ 2 on day 1. Grade 3 reduces capecitabine one level. For grade 4 diarrhea or stomatitis, oxaliplatin drops one level and capecitabine two levels. If capecitabine is discontinued, oxaliplatin is discontinued too.
• Neuropathy.
• Grade 2 persisting to the next cycle → one neurotoxicity level down.
• Grade 3 → one level down; if persistent, discontinue.
• Grade 4 → discontinue.
• Pharyngolaryngeal dysesthesia → increase the oxaliplatin infusion to 6 hours.
• Renal function (capecitabine only). CrCl > 50 mL/min → 100%. 30–50 mL/min → 75%. < 30 mL/min → discontinue.

eviQ uses percentage reductions. For example, after febrile neutropenia it advises delaying until recovery and considering a 25% reduction in both drugs. Follow your institution's protocol table.

Key trials and evidence

• XELOXA / NO16968 (Haller, JCO 2011). Adjuvant CAPOX improved disease-free survival over bolus 5-FU/folinic acid in stage III colon cancer.
• NO16966 (Cassidy, JCO 2008). First-line XELOX was non-inferior to FOLFOX-4 for progression-free survival in metastatic colorectal cancer.
• IDEA (Grothey, NEJM 2018). In low-risk stage III disease, 3 months of CAPOX was non-inferior to 6 months with much less grade ≥ 2 neuropathy. In high-risk disease, 6 months remained favoured, particularly with FOLFOX.

Clinical pearls

• Choose CAPOX for the patient, not just the disease. It suits patients who want no pump and no central line, and who will reliably stop tablets when toxicity starts. It is a poor choice for patients who cannot be relied on to stop, who have unstable renal function, or who are on warfarin without close INR access.
• "Stop and call" is part of the prescription. The single most protective instruction is to stop capecitabine at the first grade 2 toxicity (for example, 4 or more extra stools a day, or painful hands or feet) and phone the unit.
• Recalculate CrCl every cycle. Diarrhea-induced dehydration can move a patient from > 50 to 30–50 mL/min within a cycle.
• Tablet rounding matters. Doses are banded to 150 mg and 500 mg tablets. Make sure the printed tablet plan (how many of each, morning and evening) matches the order.
• Short-course adjuvant. For T1–3 N1 disease, 3 months of CAPOX is a strong evidence-based choice that spares neuropathy. Discuss it explicitly with the patient.

Educational material for health professionals and students. Not a prescribing order; it does not replace your institution's approved protocol, pharmacy verification or clinical judgement.

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