What is the CAPOX chemotherapy regimen?

The CAPOX regimen, also known as XELOX, is a combination chemotherapy protocol primarily used to treat advanced colorectal cancer, including colon and rectal cancers. It combines two medications: capecitabine (Xeloda) and oxaliplatin. The CAPOX regimen is typically delivered in cycles, each lasting 21 days (3 weeks).

What Does CAPOX Stand For?

CAPOX combines two drugs:

• CAP – Capecitabine: an oral prodrug of 5-fluorouracil.
• OX – Oxaliplatin: an intravenous platinum-based chemotherapy drug.

Both medications interfere with cancer cell DNA replication, stopping growth and spread. Capecitabine is converted in the body to 5-fluorouracil, which disrupts DNA synthesis in rapidly dividing cells, such as cancer cells. Oxaliplatin forms cross-links in DNA, preventing replication and transcription, which leads to cell death.

When Is CAPOX Used?

CAPOX is commonly used for advanced or metastatic colorectal cancer, both as initial therapy and as adjuvant (post-surgical) treatment:

• Adjuvant therapy for stage III colon cancer
• First-line treatment for metastatic colorectal cancer

It is also sometimes used for gastric, esophageal, or pancreatic cancer (off-label or trial-based). CAPOX may be preferred in patients who want to avoid central lines, since capecitabine is taken by mouth and oxaliplatin does not require central venous access.

How Is CAPOX Administered?

The CAPOX regimen is typically delivered in cycles, each lasting 21 days. The standard protocol for each cycle is as follows:

Day 1:

• Oxaliplatin is given as an intravenous infusion at a dose of 130 mg/m² over 2 hours.
• Supportive medications such as dexamethasone and ondansetron may be given to reduce side effects like nausea.

Days 1–14:

• Capecitabine is taken orally at a dose of 1,000 mg/m² twice daily (morning and evening), typically within 30 minutes after finishing a meal.

Days 15–21:

• No chemotherapy is given, allowing the patient’s body to recover before the next cycle.

This 3-week cycle is repeated, with the total number of cycles depending on the specific cancer type, stage, and treatment goals. For example, adjuvant therapy for colon cancer may involve 4–8 cycles.

How Effective Is CAPOX?

Research consistently shows that CAPOX is effective as an adjuvant and first-line treatment, with efficacy comparable to other regimens.

Effectiveness in Colon Cancer

In high-risk stage II and stage III colon cancer, CAPOX is as effective as FOLFOX for relapse-free survival, especially when used for 3 months instead of 6. The effectiveness of CAPOX has been evaluated in multiple clinical trials and real-world studies.

• One study showed a stop-and-go strategy with CAPOX (intermittent oxaliplatin) maintains similar 3-year disease-free survival (DFS) rates compared to continuous use (81.6% vs. 82.4%), while significantly reducing peripheral sensory neuropathy (15% vs. 33%).
• An observational study found that for high-risk stage II colon cancer, 3 months of CAPOX is as effective as 6 months, with equal cancer deaths and higher quality-adjusted life years (QALYs).
• One study showed 3 to 6 months of CAPOX as adjuvant therapy in patients with stage III colon cancer has 5-year DFS rates of approximately 80.7% (3 months) and 83.9% (6 months).
• Another study showed the 5-year overall survival (OS) rates are around 87% in both the 3-month and 6-month CAPOX treatment groups consisting of patients with curatively resected stage III colon cancer.
• A phase 3 randomized, controlled trial showed that the 7-year OS rate is 73% of CAPOX as adjuvant therapy in patients with stage III colon cancer and the 7-year DFS rate is 63%.
• A retrospective analysis of patients with metastatic colorectal cancer showed the disease control rate (DCR) with CAPOX is 76% overall, with a median overall survival (OS) of 19.3 months when used as first-line treatment.

Effectiveness in Rectal Cancer

• In a phase II study of locally advanced rectal cancer, 3-year relapse-free survival (RFS) was 75%, and 3-year OS was 96%.

What Are the Side Effects of CAPOX?

Common side effects of CAPOX include:

• Hand-foot syndrome (capecitabine)
• Cold sensitivity and neuropathy (oxaliplatin)
• Nausea
• Diarrhea
• Fatigue
• Myelosuppression (low blood cells)

Dose modifications or delays may be necessary in response to side effects or laboratory abnormalities, such as low white blood cell or platelet counts, or liver function changes. Supportive care may include antiemetics, hydration, antidiarrheals, and hand/foot care.

Special Considerations and Monitoring

The CAPOX regimen requires careful monitoring and individualized management to balance efficacy with toxicity. Your healthcare provider will regularly order tests and monitor you for side effects during treatment. Some tests your provider might order include:

• Liver function tests (LFTs): CAPOX can cause changes in your liver tests, which can indicate liver damage.
• Kidney tests: Capecitabine is known to cause dehydration, which can cause acute kidney failure. Additionally, you may need a dose adjustment depending on your kidney health.
• Complete blood count (CBC): CAPOX can cause a drop in your red blood cells, white blood cells, and platelets. Patients at risk of neutropenia may require treatment with granulocyte-colony stimulating factor (G-CSF).
• INR or prothrombin time: If you are taking an anticoagulant, your healthcare provider may monitor your blood work more often since capecitabine may increase your risk of bleeding.

In addition to the blood tests listed above, your healthcare provider will watch for side effects such as peripheral neuropathy (numbness and tingling in your arms or legs), lung toxicity, hand-foot syndrome, posterior reversible encephalopathy syndrome (PRES), changes in heart rhythm, skin rash or blisters, and rhabdomyolysis.

Harm to Babies

Based on animal studies, medications in CAPOX may cause harm to unborn babies when taken during pregnancy. Therefore, it is recommended to use an effective form of contraception when taking CAPOX. It is not recommended to breastfeed during treatment and for 3 months after the final dose of oxaliplatin.

Adherence to Oral Chemotherapy

While oral chemotherapy may be more convenient for some patients, it can also be harder to remember compared to receiving treatment intravenously. Make sure to set an alarm to help you remember to take your doses every day on time. This will ensure your treatment is as effective as it can be for you.

Take capecitabine within 30 minutes after a meal to decrease the occurrence of side effects. Do not cut or crush the tablets, since this can cause eye irritation, skin rash, diarrhea, and other side effects.

Summary

The CAPOX chemotherapy regimen includes capecitabine and oxaliplatin. It is a widely used and effective chemotherapy protocol for advanced colorectal and other gastrointestinal cancers. It combines oral capecitabine and intravenous oxaliplatin, administered in 3-week cycles, and is tailored to maximize efficacy while managing side effects through careful monitoring and supportive care. Common side effects include hand-foot syndrome, nausea, diarrhea, neuropathy, and low blood cells.