From the Guidelines
Capecitabine is not primarily classified as an immunosuppressive medication, but it can cause myelosuppression, leading to a secondary immunosuppressive effect due to neutropenia. It is an oral chemotherapy drug (a prodrug of 5-fluorouracil) used to treat various cancers, including breast, colorectal, and gastric cancers. While capecitabine can affect the immune system as a side effect of its mechanism of action, it does not directly suppress immune function in the way that dedicated immunosuppressants like cyclosporine, tacrolimus, or corticosteroids do. According to the study by O'Shaughnessy and colleagues 1, the addition of capecitabine to standard chemotherapy resulted in a significant improvement in overall survival (OS) in patients with triple-negative breast cancer. However, this study also reported that capecitabine can cause myelosuppression, leading to neutropenia, which can temporarily reduce the body's ability to fight infections.
The risk of significant neutropenia with capecitabine is generally lower than with intravenous 5-fluorouracil or other more aggressive chemotherapy regimens. Regular blood count monitoring is typically performed during capecitabine treatment to detect and manage any myelosuppression that may occur, as reported in the study by the Journal of Clinical Oncology 1. Patients taking capecitabine should be vigilant about signs of infection but do not require the same level of immunosuppression precautions as those on primary immunosuppressive therapies. Key points to consider when prescribing capecitabine include:
- Monitoring for myelosuppression and neutropenia
- Managing toxicity, such as hand-foot syndrome and diarrhea
- Considering the patient's age and renal function when determining the dosage
- Being aware of the potential for improved overall survival in patients with triple-negative breast cancer, as reported in the study by O'Shaughnessy and colleagues 1.
From the Research
Capecitabine and Immunosuppression
- Capecitabine is an oral prodrug of fluorouracil that is converted to its active metabolite by thymidine phosphorylase, an enzyme found in higher levels in several tumors and the liver compared to normal healthy tissue 2.
- A study published in 2021 found that capecitabine can induce T cell apoptosis, suggesting a potential immunosuppressive effect 3.
- The study found that capecitabine selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while increasing the concentration of anti-inflammatory cytokines 3.
- The immunosuppressive effect of capecitabine is thought to be due to the differential expression of thymidylate phosphorylase in cells and tissues, which allows the drug to avoid the toxic effects of myelosuppression while inducing T cell apoptosis 3.
Clinical Evidence
- Capecitabine has been shown to be effective in the treatment of various types of cancer, including breast, colorectal, and pancreatic cancer 2, 4, 5.
- The drug has a favorable toxicity profile compared to intravenous 5-fluorouracil, with a lower incidence of grade 3/4 myelotoxicity 2, 6.
- However, capecitabine can cause gastrointestinal and dermatologic effects, as well as hand-foot syndrome, which can be severe but are relatively low in incidence 2, 6.
Immunosuppressive Effects
- The immunosuppressive effects of capecitabine are thought to be related to its ability to induce T cell apoptosis, which can lead to a reduction in the proportion of T cells and the concentration of related pro-inflammatory cytokines 3.
- The clinical significance of the immunosuppressive effects of capecitabine is not fully understood and requires further study 3.