Is leucovorin needed with infusional 5-Fluorouracil (5-FU)?

From the Guidelines

Leucovorin is not always necessary with infusional 5-Fluorouracil (5-FU).

Rationale

• The QUASAR study found that 175-mg leucovorin gave similar survival and 3-year recurrence rates as 25-mg leucovorin when given with bolus 5-FU to patients as adjuvant therapy following R0 resections for CRC 1.
• Another study showed no difference in response rate or survival in patients with metastatic CRC receiving bolus 5-FU with either high-dose (500 mg/m2) or low-dose (20 mg/m2) leucovorin 1.
• If leucovorin is not available, treatment without leucovorin would be reasonable, with a possible modest increase in 5-FU dose (in the range of 10%) for patients who tolerate this without grade ≥II toxicity 1.

Infusional 5-FU Regimens

• Various infusional 5-FU regimens with or without leucovorin are used in the treatment of colorectal cancer, including simplified biweekly infusional 5-FU/LV (sLV5FU2) and weekly regimens 1.
• The choice of regimen depends on factors such as patient tolerance, disease stage, and performance status.

Key Points

• Leucovorin may not be necessary with infusional 5-FU in some cases.
• The dose of leucovorin can be reduced or omitted in certain situations, such as leucovorin shortage or patient intolerance.
• Infusional 5-FU regimens with or without leucovorin are effective in the treatment of colorectal cancer, and the choice of regimen should be individualized based on patient factors.

From the Research

Leucovorin with Infusional 5-Fluorouracil (5-FU)

• The use of leucovorin with infusional 5-FU is supported by several studies, which suggest that leucovorin can enhance the efficacy of 5-FU 2, 3, 4, 5, 6.
• In vitro experiments suggest that prolonged cellular exposure to 5-FU combined with relatively low concentrations of leucovorin provides optimal enhancement of 5-FU efficacy 2, 6.
• Clinical studies have established that 5-FU/LV regimens can yield therapeutic benefits in metastatic colorectal carcinoma, with response rates ranging from 16% to 47.2% 2, 3, 4, 5.
• Infusional 5-FU/LV regimens appear to be a strategy worthy of further clinical investigation, with potential benefits including improved efficacy and reduced toxicity 6.
• The optimal dosing and administration schedule for leucovorin with infusional 5-FU is still being investigated, with studies suggesting that low-dose leucovorin may be sufficient to modulate 5-FU 3, 5.