Trifluridine, Tipiracil

Trifluridine and tipiracil is an oral combination anticancer medicine used to treat certain advanced cancers after previous treatments have stopped working or are unsuitable. Trifluridine is a nucleoside-based antineoplastic agent that becomes incorporated into the DNA of cancer cells, interfering with DNA function and cell division. Tipiracil inhibits thymidine phosphorylase, an enzyme responsible for breaking down trifluridine. By slowing this breakdown, tipiracil increases and sustains trifluridine concentrations in the body, supporting its anticancer activity. The combination is available as film-coated tablets taken by mouth with food on specified days of a treatment cycle. It is used as a single agent for certain previously treated metastatic colorectal and gastric cancers, including adenocarcinoma of the gastroesophageal junction. It can also be combined with bevacizumab for eligible adults with metastatic colorectal cancer. The medicine is generally considered when patients have received several standard chemotherapy or targeted treatment regimens. A major safety concern is bone marrow suppression, which can reduce white blood cells, red blood cells, and platelets. Regular blood-count monitoring, careful dose adjustment, and prompt assessment of fever or signs of infection are important throughout treatment. The exact indication and regimen depend on local regulatory approval and the patient's previous therapies.

Trifluridine was initially developed as an antiviral agent, while its anticancer potential was explored through its ability to interfere with DNA synthesis. Its use as an oral cancer treatment became possible by combining it with tipiracil, which inhibits thymidine phosphorylase and reduces the breakdown of trifluridine. The combination was developed for patients with advanced gastrointestinal cancers who had limited treatment options after standard therapies. The United States Food and Drug Administration (FDA) first approved trifluridine and tipiracil in September 2015 for previously treated metastatic colorectal cancer. In February 2019, the FDA expanded its approval to include previously treated metastatic gastric or gastroesophageal junction adenocarcinoma. In August 2023, approval was expanded to allow its use in combination with bevacizumab for eligible adults with previously treated metastatic colorectal cancer. The European Commission granted marketing authorisation for Lonsurf in the European Union on 25 April 2016, with subsequent extensions to its approved uses. The European Medicines Agency (EMA) evaluates and maintains the corresponding product information. Clinical evidence supporting these indications includes the RECOURSE, TAGS, and SUNLIGHT trials. Treatment eligibility and authorised uses may vary between countries, so clinicians should follow the applicable prescribing information and local regulatory guidance, including requirements of the Central Drugs Standard Control Organisation (CDSCO) in India.

Trifluridine and tipiracil is used to treat selected adults with metastatic colorectal cancer and metastatic gastric or gastroesophageal junction adenocarcinoma after previous treatment. For metastatic colorectal cancer, it may be prescribed alone or in combination with bevacizumab when the patient has received appropriate fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and relevant biological therapies. The choice of treatment depends on previous medicines, tumour characteristics, clinical suitability, and local approval. For metastatic gastric or gastroesophageal junction adenocarcinoma, the combination is used as monotherapy in eligible patients who have received at least two previous systemic treatment regimens for advanced disease, including specified chemotherapy agents and HER2-targeted treatment when appropriate. It is generally used in later-line treatment rather than as an initial therapy. Trifluridine and tipiracil is not interchangeable with trifluridine eye drops used for certain eye infections. The oral combination should be prescribed by an oncologist familiar with its indications, dosing requirements, and blood-related toxicities.

Trifluridine and tipiracil is taken orally with food, usually twice daily on days 1–5 and days 8–12 of each 28-day treatment cycle. The standard adult starting dose is 35 mg/m² per dose, calculated using body surface area and based on the trifluridine component, up to a maximum of 80 mg per dose. The regimen generally applies when the medicine is used alone or with bevacizumab for eligible metastatic colorectal cancer and when used for metastatic gastric or gastroesophageal junction adenocarcinoma. When combined with bevacizumab for colorectal cancer, bevacizumab is administered according to its own dosing schedule and prescribing information. Tablets should be swallowed whole and should not be crushed, chewed, or split. Patients should not repeat a dose that is missed or vomited. Complete blood counts are required before treatment and during each cycle, including around day 15, to identify bone marrow suppression and guide dose interruptions or reductions. Treatment usually continues until disease progression or unacceptable toxicity, provided the patient continues to benefit. Dosing must be adjusted by the treating specialist when clinically indicated, including for significant blood-count abnormalities or certain levels of kidney impairment.

Common side effects of trifluridine and tipiracil include neutropenia, anaemia, thrombocytopenia, fatigue, nausea, reduced appetite, diarrhoea, vomiting, abdominal pain, and fever. Neutropenia can increase susceptibility to infections, anaemia may cause weakness or breathlessness, and thrombocytopenia can increase bruising or bleeding. Some patients also experience constipation, changes in taste, or general gastrointestinal discomfort. Side effects may be more pronounced in older adults or in patients with impaired kidney function, depending on their overall health and treatment regimen. When bevacizumab is added, additional adverse effects associated with that medicine must also be considered. Supportive treatment, dietary measures, anti-nausea medicines, and dose adjustments may help manage symptoms under medical supervision. Patients should report persistent vomiting or diarrhoea, marked fatigue, unusual bruising, or any fever promptly. Regular laboratory monitoring is essential because clinically important reductions in blood cell counts may occur even when symptoms are initially mild.

The principal serious risk associated with trifluridine and tipiracil is bone marrow suppression, which can cause severe neutropenia, anaemia, thrombocytopenia, and potentially life-threatening infection or bleeding. Fever or chills during treatment require prompt medical assessment, particularly when white blood cell counts are low. Treatment should be withheld, reduced, or discontinued according to the severity of toxicity and the applicable prescribing information. The medicine can also cause serious gastrointestinal toxicity, dehydration, and complications related to infection or low blood counts. It may cause fetal harm, so pregnancy status and reproductive risks should be discussed before treatment, and effective contraception should be used according to the product information. Patients with significant kidney impairment may have increased exposure or toxicity and require careful assessment and dose management. There are no general contraindications listed in the US prescribing information, but treatment may be inappropriate in certain clinical circumstances based on the patient's condition and previous reactions. Patients should not independently alter their dose or restart treatment after a significant adverse event. The oncology team should determine whether therapy can safely continue after clinical assessment and laboratory review.

Before starting trifluridine and tipiracil, clinicians should review the patient's previous cancer treatments, current medicines, kidney function, complete blood count, and overall clinical condition. Blood counts should be checked before treatment and during each cycle because neutropenia, anaemia, and thrombocytopenia may require treatment interruption or dose reduction. Patients with moderate or severe renal impairment need particular attention because toxicity may increase and dosing recommendations differ according to renal function. Liver function should also be assessed when clinically appropriate. Pregnancy should be avoided during treatment because the medicine may harm a developing fetus; contraception and fertility-related concerns should be discussed with the treating team. Breastfeeding is not recommended during treatment and for the period specified in the applicable prescribing information. When trifluridine and tipiracil is combined with bevacizumab, clinicians should also consider bevacizumab-specific precautions, including blood pressure, bleeding, and wound-healing risks. Medicines that may affect thymidine phosphorylase or cause overlapping bone marrow toxicity should be reviewed by the oncology pharmacist. Patients should inform their healthcare team about all prescription medicines, non-prescription products, and supplements before starting treatment. Any new fever, infection symptoms, or unusual bleeding requires prompt medical review.

Confirm the indication, previous treatment history, renal function, and body surface area before calculating the starting dose. Explain the treatment calendar clearly, including the scheduled dosing days and rest periods, and advise patients to take tablets with food at approximately the same times each day. Tablets should be swallowed whole, and missed or vomited doses should not be replaced with additional tablets. Arrange complete blood counts before treatment and during each cycle, including the recommended mid-cycle assessment, and establish clear instructions for reporting fever, chills, unusual bruising, bleeding, or worsening fatigue. Review renal function and other relevant laboratory results before subsequent cycles. When bevacizumab is used concurrently, coordinate monitoring and administration according to both medicines' prescribing information. Pharmacists should reinforce safe handling of cytotoxic medicines, appropriate storage, and precautions against unintended exposure. Dose interruptions and reductions should follow established protocols rather than patient-directed changes. Clear communication among the oncologist, oncology pharmacist, nursing team, and patient helps improve adherence and supports early recognition of toxicity.