Trifluridine/Tipiracil — Drug Monograph

Brand names: Lonsurf

Drug class: Antimetabolite

Mechanism of Action

Trifluridine/Tipiracil is a combination of a nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil). Trifluridine is incorporated into DNA during synthesis, which interferes with DNA function and inhibits cell proliferation. Tipiracil prevents the rapid degradation of trifluridine by thymidine phosphorylase, thereby increasing and maintaining systemic exposure of the active component. This dual mechanism overcomes some resistance patterns seen with traditional fluoropyrimidines like 5-FU.

FDA Indications

• Metastatic colorectal cancer 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

Common Side Effects

• Anemia
• Neutropenia
• Thrombocytopenia
• Fatigue
• Nausea
• Vomiting
• Diarrhea
• Decreased appetite
• Abdominal pain
• Pyrexia

Clinical Pearl

Lonsurf is often used as a late-line therapy where maintaining quality of life is paramount; its side effect profile is generally manageable but dominated by hematologic toxicity. The unique 5-days-on, 2-days-off, 5-days-on schedule is critical for patients to understand to ensure efficacy and minimize toxicity. Unlike capecitabine, hand-foot syndrome is very rare with trifluridine/tipiracil, which can be a distinguishing factor in drug selection for elderly or sensitive patients. Clinicians…

Related Therapies & Mechanisms

• 5-Fluorouracil (5-FU) (Adrucil) — Antimetabolite · CRC
• Capecitabine (Xeloda) — Antimetabolite · CRC
• Irinotecan (Camptosar) — CRC
• Mitomycin (Mitosol) — CRC