What is the use of capecitabine (Xeloda)?

From the Guidelines

Capecitabine should be used with caution, particularly in patients with hormone receptor–negative, HER2-negative breast cancer, and the dosage should be carefully considered, especially in patients ≥ 65 years old, due to higher toxicity risks 1. When considering the use of capecitabine, it's essential to weigh the potential benefits against the risks, particularly in terms of morbidity, mortality, and quality of life. The CREATE-X study, which used a dosage of 1,250 mg/m2 twice daily, showed improved recurrence-free survival and overall survival in patients with triple-negative breast cancer, but also higher toxicity rates, including hand-foot syndrome, diarrhea, and neutropenia 1.

Key Considerations

• The dosage of capecitabine used in the CREATE-X study was associated with higher toxicity in patients ≥ 65 years old 1.
• A trial-level meta-analysis of eight studies of adjuvant or neoadjuvant capecitabine added to standard chemotherapy found that capecitabine did not improve disease-free survival or overall survival in unselected patients, but did improve disease-free survival in the subset of patients with triple-negative disease 1.
• The CALGB 49907 phase III clinical trial found a 34% rate of grade 3 or higher toxicity, including two protocol-related deaths, in patients ≥ 65 years of age treated with capecitabine at a dose of 1,250 mg/m2 orally twice daily on days 1 through 14 of a 21-day cycle 1.

Dosage and Administration

• Typical dosing ranges from 1000-1250 mg/m² twice daily for 14 days, followed by a 7-day rest period, constituting a 21-day cycle.
• Patients should take capecitabine with water within 30 minutes after a meal to improve absorption and reduce stomach irritation.
• Blood counts should be monitored regularly during treatment, and patients should immediately report severe diarrhea, signs of infection, or unusual bleeding.
• Dose adjustments may be necessary based on side effects and kidney function, as the drug is primarily eliminated through the kidneys.

Side Effects

• Common side effects include hand-foot syndrome (palmar-plantar erythrodysesthesia), diarrhea, nausea, vomiting, and fatigue.
• Grade 3/4 events of interest include neutropenia, diarrhea, and hand–foot syndrome.
• Treatment discontinuation may be necessary due to adverse events.

Patient Selection

• Patients with hormone receptor–negative, HER2-negative breast cancer may benefit from capecitabine, but the dosage should be carefully considered, especially in patients ≥ 65 years old.
• Patients with triple-negative breast cancer may have improved recurrence-free survival and overall survival with capecitabine, but the risks and benefits should be carefully weighed.

From the FDA Drug Label

XELODA is a medicine you take by mouth (orally). XELODA is changed in the body to 5-fluorouracil (5-FU). XELODA is used to treat: – cancer of the colon after surgery – cancer of the colon or rectum (colorectal cancer) that has spread to other parts of the body (metastatic colorectal cancer). – breast cancer that has spread to other parts of the body (metastatic breast cancer) together with another medicine called docetaxel (Taxotere®) – breast cancer that has spread to other parts of the body and has not improved after treatment with other medicines such as paclitaxel (Taxol®) and anthracycline-containing medicine such as Adriamycin™ and doxorubicin

The main use of capecitabine is to treat:

• Colon cancer after surgery
• Metastatic colorectal cancer
• Metastatic breast cancer in combination with docetaxel or after failure of other treatments like paclitaxel and anthracycline-containing medicines 2

From the Research

Capecitabine Overview

• Capecitabine is an oral prodrug of fluorouracil, which is activated preferentially at the tumor site 3, 4.
• It has shown efficacy in the treatment of various types of cancer, including breast, colorectal, prostate, pancreatic, renal cell, and ovarian cancer 3, 4, 5.

Efficacy in Metastatic Breast Cancer

• Capecitabine has been shown to be effective in the treatment of metastatic breast cancer, both as a single agent and in combination with other therapies 4, 5, 6.
• In a phase II study, capecitabine achieved a high tumor control rate in heavily pretreated patients with metastatic breast cancer 5.
• A randomized trial compared the efficacy and tolerability of fixed-dose capecitabine with standard-dose capecitabine in metastatic breast cancer, and found that the fixed-dose schedule had less toxicity and similar efficacy 6.

Dosing Schedules

• Different dosing schedules of capecitabine have been compared in the treatment of metastatic breast cancer, including a 21-day cycle and a biweekly cycle 7.
• A single-institution experience found that alternate dosing of capecitabine (biweekly, 28-day cycle) may be a reasonable alternative to standard 21-day cycle with similar efficacy and fewer dose reductions 7.

Safety and Tolerability

• The most common adverse effects associated with capecitabine include hand-foot syndrome, diarrhea, nausea, fatigue, and hyperbilirubinemia 3, 4, 5.
• Capecitabine has been found to have a favorable safety profile compared to other therapies, with fewer instances of neutropenia, alopecia, and stomatitis 4.
• A randomized trial found that fixed-dose capecitabine had less toxicity than standard-dose capecitabine in metastatic breast cancer 6.