Not a Member?
Email this page
Send the page ""
to a friend, relative, colleague or yourself.
Separate multiple email address with a comma
We do not record any personal information entered above.
Thank you. Your email has been sent.
Other Antineoplastic Agents
Trifluridine is a nucleoside inhibitor, rapidly inactivated by thymidine phosphorylase; tipiracil inhibits thymidine phosphorylaseUsed for the treatment of metastatic colorectal cancer and metastatic gastric or gastroesophageal cancer after progression on several previous lines of chemotherapyCan cause severe myelosuppression; monitor complete blood counts and interrupt/adjust treatment as recommended
Lonsurf Oral Tab: 15-6.14mg, 20-8.19mg
35 mg/m2 based on trifluridine component (maximum, 80 mg) orally twice daily with food on days 1, 2, 3, 4, and 5, and days 8, 9, 10, 11, and 12, repeated every 28 days until disease progression or unacceptable toxicity. Round the dose to the nearest 5 mg. In a randomized, double-blind clinical trial, treatment with trifluridine; tipiracil (n = 534) significantly improved overall survival (7.1 months vs. 5.3 months) and progression-free survival (2 months vs. 1.7 months) compared with placebo in patients with heavily previously treated metastatic colorectal cancer (n = 266); all patients but one had received prior bevacizumab, and all but two KRAS wild-type patients had been previously treated with either panitumumab or cetuximab. The objective response rate (ORR) was 1.6% for trifluridine; tipiracil-treated patients and 0.4% for placebo; however, the rate of disease control was 44% vs. 16%, respectively. The addition of trifluridine; tipiracil to best supportive care also significantly delayed the time to worsening of ECOG performance status to 2 or higher (5.7 months vs. 4 months). 
35 mg/m2 based on trifluridine component (maximum, 80 mg) orally twice daily with food on days 1, 2, 3, 4, and 5, and days 8, 9, 10, 11, and 12, repeated every 28 days until disease progression or unacceptable toxicity. Round the dose to the nearest 5 mg. In a randomized, double-blind clinical trial, treatment with trifluridine; tipiracil significantly improved median overall survival (5.7 months vs. 3.6 months) compared with placebo in patients with heavily pretreated metastatic gastric or gastroesophageal junction cancer. Median progression-free survival was also significantly improved but amounted to a difference of only 0.2 months (2 months vs. 1.8 months). Grade 3 or higher adverse reactions occurred in 79.4% of patients in the treatment arm compared with 57.7% in the placebo arm.
160 mg (trifluridine component) PO total daily dose (80 mg PO administered twice daily) on days 1, 2, 3, 4, 5 and days 8, 9, 10, 11, 12, repeated every 28 days.
Safety and efficacy have not been established.
Baseline Hepatic Impairment:Mild hepatic impairment (total bilirubin less than or equal to upper limit of normal (ULN) and AST greater than ULN; OR total bilirubin 1.1 to 1.5 times ULN and any AST): No adjustment to the starting dose is recommended.Moderate to severe hepatic impairment (total bilirubin level greater than 1.5 times ULN and any AST): Do not administer trifluridine; tipiracil.
Baseline Renal Impairment:Mild to moderate renal impairment (CrCL 30 mL/min or higher): No adjustment to the starting dose is recommended.Severe renal impairment (CrCL less than 30 mL/min): Specific guidelines are not available as these patients were excluded from clinical trials.
Take with food.Swallow tablets whole. Do not crush or chew tablets; round dose to the nearest 5-mg increment.Do not take additional doses to make up for doses that are vomited or missed.When handling medication, wear gloves and wash hands afterward.
Lonsurf:- If stored outside of original bottle, discard after 30 days- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
Trifluridine; tipiracil is associated with severe bone marrow suppression including neutropenia, anemia, and thrombocytopenia; do not begin a course of therapy if the ANC is less than 1,500 cells/mm3 or platelets are less than 75,000 cells/mm3. Obtain complete blood counts prior to and on day 15 of each cycle, and more frequently as clinically indicated; an interruption or delay of therapy may be necessary for myelosuppression or neutropenic fever. In clinical trials, geriatric patients (65 years and older) had a higher incidence of grade 3 and 4 hematologic toxicity than patients younger than 65 years. Patients who have had previous myelosuppressive therapy such as chemotherapy or radiation therapy are also at risk of increased bone marrow suppression during trifluridine; tipiracil treatment. Patients with an active infection should be treated prior to receiving trifluridine; tipiracil. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy. Patients should immediately report any symptoms of severe myelosuppression such as fever, sore throat, or abnormal bleeding.
The safety and effectiveness of trifluridine; tipiracil have not been established in children younger than 18 years of age or infants. Dental toxicity including whitening, breakage, and malocclusion (degeneration and disarrangement in the ameloblasts, papillary layer cells, and odontoblasts) were observed in rats treated with trifluridine; tipiracil at approximately 0.33 times the exposure in humans at the clinical dose of 35 mg/m2 twice daily.
Pregnancy should be avoided by females of reproductive potential during trifluridine; tipiracil treatment and for at least 6 months after the last dose. Although there are no adequately controlled studies in pregnant animals or humans, trifluridine; tipiracil can cause fetal harm or death when administered during pregnancy based on its mechanism of action and animal studies. Women who are pregnant or who become pregnant while receiving trifluridine; tipiracil should be apprised of the potential hazard to the fetus. When administered once daily to female rats during organogenesis, decreased fetal weight was observed at approximately 0.33 times the exposure achieved with the recommended dosing. Embryolethality and structural abnormalities (kinked tail, cleft palate, ectrodactyly, anasarca, alterations in great vessels, and skeletal abnormalities) occurred at exposures 0.92 times that achieved with the recommended dose.
Counsel patients about the reproductive risk and contraception requirements during trifluridine; tipiracil treatment. Trifluridine; tipiracil can be teratogenic if taken by the mother during pregnancy. Females should avoid pregnancy and use effective contraception during treatment with trifluridine; tipiracil and for at least 6 months after the last dose. Because of the potential for male-mediated teratogenicity, males with female partners taking trifluridine; tipiracil should use effective contraception during treatment and for at least 3 months after the last dose. Females of reproductive potential should undergo pregnancy testing prior to initiation of trifluridine; tipiracil. Women who become pregnant while receiving trifluridine; tipiracil or while their male partner is being treated should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of trifluridine; tipiracil on human fertility, there was not an effect on male or female fertility in animal studies.
It is not known whether trifluridine; tipiracil is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, females should avoid breast-feeding during treatment and for 1 day after the final dose.
neutropenia / Delayed / 32.0-46.0anemia / Delayed / 16.0-22.0anorexia / Delayed / 4.0-9.0thrombocytopenia / Delayed / 4.0-7.0asthenia / Delayed / 0-7.0fatigue / Early / 0-7.0infection / Delayed / 0-5.0vomiting / Early / 2.0-4.0pulmonary embolism / Delayed / 2.0-3.1nausea / Early / 2.0-3.0diarrhea / Early / 3.0-3.0abdominal pain / Early / 0-2.0fever / Early / 0-1.0stomatitis / Delayed / 0-1.0
pneumonitis / Delayed / 0.2-0.2bone marrow suppression / Delayed / Incidence not knownQT prolongation / Rapid / Incidence not known
dysgeusia / Early / 0-7.0alopecia / Delayed / 0-7.0
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents. Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity. Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Trifluridine is a thymidine-based nucleoside metabolic inhibitor, believed to act as a thymidylate synthase inhibitor (similar to 5-fluorouracil). Following uptake into cancer cells, it is incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation. Tipiracil increases trifluridine exposure by inhibiting thymidine phosphorylase, which is responsible for rapid inactivation of trifluridine after administration. Trifluridine; tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in mice. 
Trifluridine; tipiracil is administered orally. Trifluridine is highly protein bound (greater than 96%) to human serum albumin, independent of drug concentration and the presence of tipiracil. The plasma protein binding of tipiracil is less than 8%. After twice daily dosing, systemic exposure of trifluridine increased more than dose-proportionally over a range of 15 mg/m2 to 35 mg/m2. After a single dose, the mean half-life of trifluridine is 1.4 hours and tipiracil is 2.1 hours when administered in combination; at steady state, the mean half-lives are 2.1 hours and 2.4 hours, respectively. When trifluridine was administered as an intravenous single agent, the half-life was 12 minutes. Trifluridine is mainly eliminated via thymidine phosphorylase metabolism to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY); tipiracil is not metabolized in either human liver or hepatocytes. No other metabolites were detected in plasma or urine. Following a single oral 60-mg dose of trifluridine; tipiracil with radiolabeled trifluridine, 60% of the radioactivity was recovered within 24 hours, including 55% of the dose in the urine (as FTY and trifluridine glucuronide isomers), less than 3% of the dose in the feces, and less than 3% of the dose in expired air. Unchanged trifluridine accounted for less than 3% of the administered dose recovered in the urine and feces. Following a single oral 60-mg dose of trifluridine; tipiracil with radiolabeled tipiracil, 77% of the radioactivity was recovered, including 27% of the dose excreted in the urine and 50% of the dose excreted in the feces. Tipiracil was the major component and 6-HMU was the major metabolite in the urine and feces. Affected CYP450 isoenzymes or other drug transporters: None.Trifluridine and tipiracil are not metabolized by cytochrome P450 (CYP450) enzymes.
After a single dose administered to patients with cancer, the Tmax of trifluridine; tipiracil was approximately 2 hours. Administration of a single dose of trifluridine; tipiracil 35 mg/m2 increased the mean Cmax of trifluridine by 22-fold and AUC by 37-fold, with reduced variability, compared to trifluridine 35 mg/m2 alone. The accumulation of trifluridine at steady-state was 2-fold for Cmax and 3-fold for AUC; no accumulation was observed for tipiracil. The Cmax of both trifluridine and tipiracil as well as the AUC of tipiracil were decreased by approximately 40% by a standardized high-fat, high-calorie meal in patients with cancer compared to those in a fasting state; the AUC of trifluridine did not change with food. The recommendation to take trifluridine; tipiracil with meals is based on an observed correlation between an increase in Cmax and a decrease in neutrophil counts.