Trifluridime/tipiracil (Lonsurf)

Oral medication combination of trifluridine and tipiracil.

Lonsurf, trade name.

Trifluridine is an oral  bioavailable thymidine based nucleoside analogue.

It is phosphorylated by thymidylate kinase to produce trifluridine mono and triphosphate derivatives, both of which inhibit the proliferation of tumor cells.

Trifluridine monophosphate irreversibly inhibits thymidylate synthase and trifluorine triphosphate is incorporated into DNA and when incorporated it  damages DNA,  causing cell death.

For use in the treatment of unresectable advanced or recurrent colorectal cancer.

Indicated for the treatment of patients with metastatic colorectal cancer (mCRC) 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.

An oral therapy for metastatic colorectal cancer.

Combines a thymidine analog, trifluridine, which is the active cytotoxic part of the combination after its incorporation and binding into DNA with a thymidine phosphorylase inhibitor, tipiracil, which mitigates trifluridine catabolism and increases its availability and antitumor activity.

For patients with mCRC who have been previously treated with:




Anti-VEGF biological therapy

Anti-EGFR therapy (if RAS wild type).

Anti-vascular growth factor biological product, and an anti–epidermal growth factor receptor EGFR monoclonal antibody.

Triflluridine is a thymidine based nucleoside analogue that is metabolized to the triphosphate metabolite, which is then incorporated into DNA, resulting in inhibition of DNA synthesis and function.

Triflluridine monophosphate inhibits thymidylate synthase which is the key enzyme provides for the sole intracellular source of thymidylate in the essential nucleotide precursor for DNA biosynthesis.

Recommended to have complete blood counts prior to and on day 15 of each cycle and more frequently as clinically indicated.

Patients with moderate renal impairment may require dose modifications.

The combination of two active ingredients ― trifluridine, a nucleoside analogue, and tipiracil hydrochloride, a thymidine phosphorylase inhibitor, which prevents the rapid metabolism of trifluiridine, thereby increasing its bioavailability.

Efficacy and safety were evaluated in the phase 3 RECOURSE trial, an international, randomized, double-blind study involving 800 patients with previously treated metastatic colorectal cancer.

In the above study the median overall survival, was 7.1 months with Lonsurf vs 5.3 months with placebo, and the progression-free survival, which was 2 months with Lonsurf vs 1.7 months with placebo.

Most common side effects are anemia, neutropenia or thrombocytopenia, physical weakness, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and fever.

Can cause severe and life-threatening myelosuppression.

Neutropenia associated with better survival.

Thrombocytopenia has only a 5% risk.

It is taking within one hour of a.m. and p.m. meals: Initially 35 mg meter squared twice daily on days 1 through 5 and 8 through 12 of each 28 day cycle until disease progression or unacceptable toxicity.

Maximum dose 80 mg based on trifluridine component.

Trifluridine, tipracil:15mg/6.14 mg.

Tipiracil is a thymidine phosphorylase inhibitor, which inhibits trifluridine degradative metabolism by thymidine phosphorylase, and this elevation leads to enhanced the activation of trifluridine to the monophosphate and triphosphate cytotoxic metabolites.

Efficacy of Trifluridine/ Tipiracil Improved With Bevacizumab in Chemo-Refractory mCRC

In patients with chemo-refractory metastatic colorectal cancer (mCRC), trifluridine/tipiracil (FTD/TPI) with or without bevacizumab demonstrated a significant and clinically relevant improvement in survival compared with FTD/TPI monotherapy

FTD/TPI was administered orally at the dose of 35 mg/m2/dose bid from days 1 to 5 and 8 to 12 in the first arm, and the same dose of FTD/TPI was combined with bevacizumab at a dose of 5 mg/kg on day 1 and on day 15 of a 28-day treatment cycle in the second arm.

Median PFS was significantly improved in the arm that received FTD/TPI plus bevacizumab compared with the arm that received FTD/TPI alone, and the median overall survival (OS) was significantly prolonged with FTD/TPI plus bevacizumab vs FTD/TPI alone (9.4 months vs 6.7 months, respectively.

Now approved for the treatment of adults with metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received ≥2 previous lines of chemotherapy that included a fluoropyrimidine, a platinum, a taxane or irinotecan, and (if appropriate) a HER2/neu-targeted therapy.

TAGS clinical trial of 507 patients with metastatic gastric or GEJ adenocarcinom¡a who were previously treated with ≥2 lines of chemotherapy were randomized in a 2:1 ratio to receive trifluridine/tipiracil 35 mg/m2 plus best supportive care or placebo with best supportive care until disease progression or unacceptable toxicity occurred: The median overall survival was 5.7 months versus 3.6 months for patients receiving trifluridine/tipiracil and placebo.

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