Trifluridine + Tipiracil

Indications

Trifluridine + Tipiracil is used for: Indicated for treatment of patients with, metastatic colorectal cancer, Gastric Cancer

Adult Dose

Oral Colorectal Cancer Indicated for treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy (if RAS wild-type) Dose is based on trifluridine component rounded to the nearest 5-mg increment 35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose Continue until disease progression or unacceptable toxicity Gastric Cancer Indicated for treatment of patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with ?2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy Dose is based on trifluridine component rounded to the nearest 5-mg increment 35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose Continue until disease progression or unacceptable toxicity Hepatic impairment Mild (total bilirubin [TB] ULN, or TB <1-1.5x ULN and any AST): No dosage adjustment required Moderate-to-severe: Not studied

Child Dose

Renal Dose

Renal impairment Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required; however, patients with moderate impairment (30-59 mL/min) may require dose modification for increased toxicity Severe (CrCl <30 mL/min): Not studied

Administration

Oral Administration Dose is based on trifluridine component rounded to nearest 5-mg increment Administer with food; swallow whole Do not take additional doses to make up for missed or held doses

Contra Indications

Precautions

Severe and life-threatening myelosuppression reported, including anemia, neutropenia, thrombocytopenia, and febrile neutropenia; obtain CBC count prior to and on Day 15 of each cycle, or more frequently as indicated Based on animal studies and its mechanism of action, trifluridine/tipiracil can cause fetal harm when administered to pregnant women

Pregnancy-Lactation

Pregnancy Based on animal data and its mechanism of action, drug can cause fetal harm Embryo-fetal lethality and embryo-fetal toxicity occurred in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose There are no available data use in pregnant women Verify pregnancy status in females of reproductive potential before initiating treatment Contraception Females of reproductive potential: Use effective contraception during treatment and for >6 months after final dose Males with female partners of reproductive potential: Use condoms during treatment and for >3 months after final dose Lactation There are no data on the presence of trifluridine, tipiracil or its metabolites in human milk or its effects on the breastfed child or on milk production In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 day following the final dose

Interactions

Adverse Effects

Side effects of Trifluridine + Tipiracil : >10% (Metastatic Colorectal Cancer) Anemia (77%) Neutropenia (67%) Asthenia/fatigue (52%) Nausea (48%) Thrombocytopenia (42%) Decreased appetite (39%) Neutropenia, Grade 3 or 4 (38%) Diarrhea (32%) Vomiting (28%) Infections (27%) Pyrexia (19%) Anemia, Grade 3 or 4 (18%) >10% (Metastatic Gastric Cancer) Neutropenia (66%) Anemia (63%) Neutropenia, Grade 3 or 4 (38%) Nausea (37%) Decreased appetite (34%) Thrombocytopenia (34%) Vomiting (25%) Diarrhea (23%) Infections (23%) Anemia, Grade 3 or 4 (19%)

Mechanism of Action

Trifluridine: Thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation Tipiracil: Thymidine phosphorylase inhibitor; inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase