Should Xelox (capecitabine and oxaliplatin) be discontinued in a patient with stage IIIB rectosigmoid cancer (Ca rectosigmae) with elevated aspartate aminotransferase (AST) levels following surgery?

From the Guidelines

XELOX therapy should not be discontinued immediately in a patient with elevated AST levels (100 U/L) during adjuvant treatment for stage IIIB rectal cancer, but rather, a dose reduction of capecitabine by 25-50% should be considered while closely monitoring liver function tests weekly 1. The patient's current AST level, approximately 3 times the upper limit of normal, indicates grade 1 hepatotoxicity, which can often be managed with dose adjustments rather than cessation of therapy. Given the importance of maintaining treatment continuity to prevent recurrence in stage III colorectal cancer, as emphasized by the Chinese Society of Clinical Oncology guidelines 1, modifications to the treatment regimen are preferable to discontinuation. Key considerations include:

• Monitoring liver function tests weekly to assess the impact of dose reduction
• Ensuring the patient is well-hydrated and avoiding alcohol and hepatotoxic medications
• Considering consultation with a hepatologist if liver function deteriorates despite dose adjustments
• Recognizing that both capecitabine and oxaliplatin can cause hepatotoxicity, with capecitabine being the more common cause The current guidelines support the use of combination chemotherapy regimens like CAPEOX (XELOX) for stage III patients, highlighting the importance of balancing the benefits of treatment against potential toxicities 1.

From the FDA Drug Label

Discontinue treatment unless treating physician considers it to be in the best interest of the patient to continue with XELODA at 50% of original dose. Therapy with XELODA should be interrupted upon the occurrence of a grade 2 or 3 adverse experience Table 19 Recommended Dose Modifications With XELODA Monotherapy Toxicity NCIC Grades*During a Course of TherapyDose Adjustment for Next Treatment (% of starting dose) • Grade 1Maintain dose levelMaintain dose level • Grade 2 -1st appearanceInterrupt until resolved to grade 0-1100% -2nd appearanceInterrupt until resolved to grade 0-175% -3rd appearanceInterrupt until resolved to grade 0-150% -4th appearanceDiscontinue treatment permanently • Grade 3 -1st appearanceInterrupt until resolved to grade 0-175% -2nd appearanceInterrupt until resolved to grade 0-150% -3rd appearanceDiscontinue treatment permanently

The patient's AST (Aspartate Aminotransferase) level is 100 U/L, which is above the normal range (<35 U/L), indicating a potential grade 2 or 3 toxicity. According to the dose modification guidelines in Table 19, if a grade 2 toxicity occurs for the 1st appearance, the treatment should be interrupted until resolved to grade 0-1, and then resumed at 100% of the original dose. However, if a grade 3 toxicity occurs for the 1st appearance, the treatment should be interrupted until resolved to grade 0-1, and then resumed at 75% of the original dose. Since the exact grade of toxicity is not specified, and considering the elevated AST level, it is recommended to interrupt the XELODA treatment until the AST level resolves to grade 0-1. After resolution, the treatment can be resumed at a reduced dose, depending on the grade of toxicity, as per the guidelines in Table 19 2.

From the Research

Elevated AST Levels and Xelox Treatment

• The patient's AST level is elevated at 100 U/l, which is above the normal range of <35 U/l 3.
• Elevated AST levels can indicate liver damage, but AST is also present in cardiac and skeletal muscle and in erythrocytes, making ALT a more specific marker for liver damage 3.
• There is no direct evidence in the provided studies to suggest that elevated AST levels alone are a reason to discontinue Xelox treatment.

Xelox Treatment and Liver Function

• Xelox is a combination of capecitabine and oxaliplatin, which is a safe and active first-line regimen for older patients with metastatic colorectal cancer 4.
• The feasibility of XELOX without a central venous access device has been evaluated in patients with stage III colorectal cancer, and it was found to be a feasible approach for treating patients in the adjuvant setting 5.
• However, the studies do not provide specific guidance on how to manage elevated AST levels in patients receiving Xelox treatment.

Management of Abnormal Liver Test Results

• A systematic, stepwise approach to the evaluation and management of abnormal liver test results is recommended to optimize high-value care 6.
• The pattern and severity of liver injury may provide clues about the cause of disease and should guide diagnostic evaluation with serologic testing and liver imaging 6.
• It is essential to interpret abnormal liver test results in the context of the patient's history and examination, rather than relying solely on laboratory thresholds 6.

Decision to Discontinue Xelox

• The decision to discontinue Xelox treatment should be based on a comprehensive evaluation of the patient's condition, including the severity of the elevated AST levels, the presence of any symptoms, and the potential benefits and risks of continuing treatment.
• It is recommended to consult the relevant clinical guidelines and expert opinions to determine the best course of action for managing elevated AST levels in patients receiving Xelox treatment 4, 5, 6.