Adherence, Dosing, and Managing Toxicities With Trifluridine/Tipiracil (TAS-102)

Abstract

Trifluridine/tipiracil (TAS-102) is a new oral combination therapy approved by the US Food and Drug Administration for the treatment of patients with metastatic colorectal cancer who are refractory to or intolerant of standard chemotherapy. This agent consists of a thymidine-based nucleoside analog (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil), which is included to reduce the degradative breakdown of trifluridine. In the phase 3 RECOURSE trial, trifluridine/tipiracil showed significant improvement in overall survival when compared with placebo. Trifluridine/tipiracil is administered at 35 mg/m2/dose orally twice daily in a 28-day cycle consisting of 5 treatment days/2 rest days for 2 weeks followed by a rest period of 2 weeks. Because trifluridine/tipiracil is a completely oral chemotherapy regimen, patient adherence to treatment is an important consideration. It is also critical to have strategies in place for managing toxicities, as side effects may have a negative impact on patient adherence. The most frequent adverse events reported in patients with metastatic colorectal cancer receiving trifluridine/tipiracil in the phase 3 RECOURSE trial were myelosuppression, nausea/vomiting, diarrhea, decreased appetite, and fatigue. This review aims to provide clinicians with practical recommendations for facilitating patient adherence to oral chemotherapy, managing trifluridine/tipiracil dosing, and addressing the most common adverse events in patients receiving trifluridine/tipiracil therapy.

Further Therapeutic Options in Heavily Pretreated Colorectal Cancer Patients

“…Hematologic toxicities, including leukopenia, neutropenia, and anemia, and gastrointestinal toxicities, such as nausea/vomiting, diarrhea, and the loss of appetite, as well as fatigue of various grade, were the most frequent side effects observed in patients treated with trifluridine/tipiracil [40][41][42][43][44][45]. The most common grade 3/4 toxicity was myelosuppression (neutropenia, anemia, febrile neutropenia) [46].…”

New Drug Combination in Colorectal Cancer Treatment: Trifluridine and Tipiracil

“…15 TF-TMP, DNA biyosentezinin temel bir nükleotit öncüsü olan timidilatın hücre içi tek kaynağı, anahtar enzimi olan timidilat sentazı (TS) inhibe eder. 11 Trifluridin monofosfat (TF-TMP), tirozinin 146 aktif bölgesine direkt bağlanarak TS'ı inhibe eder, 2'-Deoksiüridin-5'-monofosfat'ın (dUMP) 2'-deoksitimidin-5'-monofosfat'a (dTMP) metilasyonunu önler ve pirimidin sentezini engeller. Deoksiüridin-5'-monofosfat (dUMP), trifosfat for- Hücrelerdeki TF-TMP ayrıca enzimatik olarak, trifluridin trifosfata (TF-TTP) fosforile edilir, bu da doğrudan DNA'ya dahil edilir.…”

“…Bu inhibisyon, trifluridin'in monofosfat ve trifosfat sitotoksik metabolitlerinin aktivasyonunun artmasına yol açar. 11 Timidin fosforilaz (TP), kanser metastazı sıra-sında endotel hücrelerinin çoğalmasını kolaylaştır-dığı için tümör anjiyojenezine de önemli bir katkıda bulunur. Tümör anjiyojenezi terimi ile, solid tümörlerin büyümesi ve metastazı sırasında önceden var olan damarlardan yeni kan damarlarının gelişimi kastedilir.…”

Beneficial Treatment Management with Trifluridine/Tipiracil in a Patient with Metastatic Colorectal Cancer and Pronounced Hematological Event History during Previous Treatments

“…Due to this hematotoxicity profile, it remains a great challenge for physicians to transfer the FTD/TPI administration into clinical settings with mCRC patients that had already had manifestations of serious hematological events along their treatment history. In this report, we present an mCRC case in which these hematological events could be managed successfully by means of dose reduction and treatment delay as well as preventive granulocyte colony-stimulating factor (G-CSF) administration [ 6 , 7 ].…”