What are the clinical uses and dosing regimens for Trifluridine?

From the Guidelines

Trifluridine is primarily used in combination with Tipiracil for the treatment of metastatic colorectal cancer, with a recommended dosing regimen of 35 mg/m2 (maximum single dose 80mg), orally, twice a day, on days 1-5 and 8-12, repeated every 28 days 1.

Clinical Uses

• Trifluridine/Tipiracil is used for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy regimens and who have previously received or are not suitable for anti-VEGF treatment and anti-EGFR treatment (RAS wild-type) 1.
• The combination of Trifluridine/Tipiracil and Bevacizumab has also been studied in the non-first-line setting, showing improved overall survival and progression-free survival compared to Trifluridine/Tipiracil monotherapy 1.

Dosing Regimens

• The recommended dosing regimen for Trifluridine/Tipiracil is 35 mg/m2 (maximum single dose 80mg), orally, twice a day, on days 1-5 and 8-12, repeated every 28 days 1.
• Alternative dosing regimens include Trifluridine/Tipiracil 35 mg/m2 (maximum single dose 80mg), orally, twice a day, on days 1-5, repeated every 14 days, in combination with Bevacizumab 5 mg/kg, intravenous infusion, on day 1, repeated every 14 days 1.

Important Considerations

• Trifluridine/Tipiracil is an orally administered drug, and patients should be instructed to take the medication as directed, with or without food 1.
• The most common adverse events associated with Trifluridine/Tipiracil include neutropenia, leukopenia, and febrile neutropenia, and patients should be monitored closely for these adverse events 1.

From the FDA Drug Label

INDICATIONS AND USAGE LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with: metastatic colorectal cancer as a single agent or in combination with bevacizumab who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

DOSAGE AND ADMINISTRATION Recommended Dosage: 35 mg/m2/dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle.

The clinical uses of Trifluridine are:

• Treatment of metastatic colorectal cancer as a single agent or in combination with bevacizumab
• Treatment of metastatic gastric or gastroesophageal junction adenocarcinoma The dosing regimen for Trifluridine is:
• 35 mg/m2/dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle 2

From the Research

Clinical Uses of Trifluridine

• Trifluridine is used in combination with tipiracil for the treatment of adult patients with metastatic colorectal cancer (mCRC) who are refractory to or are not considered candidates for current standard chemotherapy and biological therapy 3.
• The combination of trifluridine/tipiracil with bevacizumab has shown efficacy in the third-line setting for mCRC, with a manageable toxicity profile 4, 5.
• Trifluridine/tipiracil has been approved for the treatment of unresectable advanced or recurrent colorectal cancer in Japan 3.

Dosing Regimens for Trifluridine

• The approved regimen for oral trifluridine/tipiracil is 35 mg/m(2) twice daily on days 1-5 and 8-12 of each 28-day cycle 3.
• A biweekly regimen of trifluridine/tipiracil has been investigated, with preliminary results showing prolonged overall survival and progression-free survival compared to the standard regimen 6.
• The combination of trifluridine/tipiracil with bevacizumab is being studied in the SUNLIGHT trial, with a primary objective of improving overall survival compared to trifluridine/tipiracil monotherapy 5.

Adverse Events Associated with Trifluridine

• Common adverse events associated with trifluridine/tipiracil include anaemia, neutropenia, thrombocytopenia, and leukopenia 3.
• Asthenia and neutropenia are also common adverse events, with a frequency of 48.1% each 7.
• The biweekly regimen of trifluridine/tipiracil has been associated with a similar adverse event profile to the standard regimen, with no significant differences in adverse events between the two groups 6.