Can FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) be used in the setting of hepatic impairment?

From the Guidelines

FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) can be used in the setting of hepatic impairment, but its use requires careful consideration of the patient's overall condition and liver function.

Key Considerations

• For patients with mild hepatic impairment, FOLFOX can be administered at standard doses, but close monitoring is necessary 1.
• The evidence does not provide clear guidance on dose adjustments for moderate hepatic impairment, but it is generally recommended to reduce the oxaliplatin dose by 25-50% in such cases.
• In severe hepatic impairment, FOLFOX is generally not recommended due to the increased risk of toxicity, but there is limited direct evidence to support this recommendation in the context of FOLFOX use.

Clinical Context

In clinical practice, the decision to use FOLFOX in patients with hepatic impairment should be based on a thorough evaluation of the patient's condition, including their performance status, liver function tests, and extent of liver disease.

• Patients with good performance status (e.g., ECOG 0-1) and mild hepatic impairment may be candidates for FOLFOX at standard doses, while those with poor performance status (e.g., ECOG 2) or severe hepatic impairment may require alternative treatments or dose adjustments 1.
• The use of FOLFOX in patients with hepatic impairment has been explored in the context of hepatocellular carcinoma, where it has shown promise as a treatment option, particularly in combination with other therapies 1.

Dosing and Administration

The dosing and administration of FOLFOX in patients with hepatic impairment should be individualized based on the patient's condition and liver function.

• The standard dose of FOLFOX consists of oxaliplatin 85-130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2, and 5-fluorouracil 2,400 mg/m2 for 46 hours or 24 hours, but dose adjustments may be necessary in patients with hepatic impairment 1.
• Close monitoring of liver function tests and adverse effects is essential to ensure safe use of FOLFOX in patients with hepatic impairment.

From the Research

FOLFOX in Hepatic Impairment

• FOLFOX (Folinic acid, Fluorouracil, Oxaliplatin) can be used in patients with hepatic impairment, as evidenced by several studies 2, 3, 4, 5.
• These studies demonstrate that FOLFOX can be effective in treating metastatic colorectal cancer with severe liver dysfunction, with minimal toxicity 2, 3, 4, 5.
• The safety and feasibility of FOLFOX in patients with severe liver dysfunction secondary to liver metastases of colorectal cancer have been supported by multiple case reports 2, 3, 4, 5.

Dosing and Toxicity

• Dose reductions of 5-FU and oxaliplatin may be necessary in patients with severe liver dysfunction, as seen in one study where a 50% dose reduction of 5-FU bolus and a 15% dose reduction of oxaliplatin were used 2.
• Toxicity profiles have been acceptable in patients with hepatic impairment, with grade 2 stomatitis being the only significant toxicity reported in one study 2.
• Other studies have also reported minimal toxicity, with improvements in liver function tests and clinical outcomes 3, 4, 5.

Comparison with Other Regimens

• One study compared the effectiveness and safety of FOLFOX with another regimen, RALOX, in patients with intermediate and advanced hepatocellular carcinoma, and found similar outcomes and toxicity profiles 6.
• However, this study was not directly related to the use of FOLFOX in patients with hepatic impairment due to colorectal cancer metastases.