Search results for "Tipiracil"
showing 10 items of 12 documents
Duration of previous treatment as a prognostic factor in metastatic colorectal cancer treated with trifluridine/tipiracil
2018
We herein describe the findings from the trifluridine/tipiracil (TAS-102) Compassionate Use program in Latvia, set up prior to marketing authorization for the management of pretreated patients with metastatic colorectal cancer (mCRC). The efficacy and safety of TAS-102 in patients with refractory mCRC were evaluated in the phase III trial RECOURSE. A previous report confirmed neutropenia and duration of previous treatment for mCRC as prognostic factors in TAS-102 users. The aim of the present study was to analyze possible prognostic factors, such as neutropenia, in TAS-102 responders. A retrospective analysis of 14 patients who received TAS-102 chemotherapy in two institutions in Latvia (Cl…
Trifluridine/tipiracil : an emerging strategy for the management of gastrointestinal cancers
2018
Fluoropyrimidines are currently the backbone of treatment for gastrointestinal (GI) cancers but development of resistance to these agents remains a major problem. Trifluridine/tipiracil is an oral chemotherapeutic agent recently approved for third-line treatment of chemorefractory metastatic colorectal cancer. This article reviews the clinical value of trifluridine/tipiracil as a monotherapy, including recent trials in GI cancers, and the potential benefit of combining it with other agents in patients with GI cancers, including the preclinical rationale for combination therapy and recently completed and ongoing clinical trials. Data gathered so far suggest that trifluridine/tipiracil has t…
A phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in metastatic colorectal cancer.
2017
TPS3626 Background: Trifluridine/tipiracil, also known as TAS‐102, is a combination of an antineoplastic thymidine‐based nucleoside analogue (trifluridine) and a thymidine phosphorylase inhibitor (tipiracil hydrochloride). The antitumor activity of combined trifluridine/tipiracil and oxaliplatin has been studied in gastrointestinal tumor xenografts, including a 5‐FU resistant subline, using a nude mouse model. This study demonstrated increased antitumor activity for the combination compared to trifluridine/tipiracil or oxaliplatin alone (p < 0.001) (Nukatsuka et al., Anticancer Res 2015). These data support the rationale for clinical use of the combination. We describe a phase 1, intern…
Phase I multicenter, open-label study to establish the maximum tolerated dose (MTD) of trifluridine/tipiracil (TAS-102) and oxaliplatin combination i…
2018
816 Background: Preclinical evidence suggests improved efficacy when combining trifluridine/tipiracil with oxaliplatin compared to each monotherapy (Nukatsuka, 2015). The primary objective was to determine the MTD and the safety profile of the doublet among mCRC pts who have progressed after at least one prior line of treatment. Methods: Using a 3+3 design, eligible pts received escalating trifluridine/tipiracil doses from 25, 30 to 35 mg/m² bid, days 1–5 q14, together with a fixed dose of oxaliplatin 85 mg/m² (day 1). An intermediate cohort with a lower dose of oxaliplatin (65 mg/m²) plus 35 mg/m² of trifluridine/tipiracil was also tested. Results: Fifteen of 17 enrolled pts were evaluabl…
ESMO consensus guidelines for the management of patients with metastatic colorectal cancer
2016
Contains fulltext : 165965.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and speciali…
Phase I dose-escalation of trifluridine/tipiracil in combination with oxaliplatin in patients with metastatic colorectal cancer
2019
Abstract Background and objectives Pre-clinical data have shown that combining trifluridine/tipiracil with oxaliplatin enhances anti-tumour activity compared with either monotherapy. A phase I dose-escalation study was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD) for phase II and pharmacokinetic profile of this combination in patients with metastatic colorectal cancer (mCRC) who had progressed after at least 1 prior line of treatment. Methods Using a 3 + 3 design, patients received escalating trifluridine/tipiracil doses from 25, then 30 and to 35 mg/m2 twice daily, days 1–5, q14 days, together with a fixed dose of 85 mg/m2 of oxaliplatin day 1, q14 days. A…
A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
2021
Aim: To determine a recommended Phase II dose of the oral fluoropyrimidine trifluridine/tipiracil (FTD/TPI) combined with the multi-kinase inhibitor regorafenib (REG) in refractory metastatic colorectal cancer patients. Materials & methods: A conventional 3 + 3 dose finding design was used. FTD/TPI was administered on days 1–5 and 8–12 of a 28-day cycle, REG on days 2–22. Two dose levels were used: FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d, then escalated to FTD/TPI 35 mg/m2 b.i.d. + REG 120 mg/d. Results: In total, 12 patients were treated at two dose levels. Three dose-limiting toxicities were observed; all were grade 3 hypertension causally attributed to REG. Recommended Phase II dose …
Efficacy of trifluridine and tipiracil (TAS-102) versus placebo, with supportive care, in a randomized, controlled trial of patients with metastatic …
2016
[Purpose] TAS-102 is a combination of the thymidine-based nucleoside analog trifluridine and the thymidine phosphorylase inhibitor tipiracil. Efficacy and safety of TAS-102 in patients with metastatic colorectal cancer (mCRC) refractory or intolerant to standard therapies were evaluated in the phase 3 RECOURSE trial. Results of RECOURSE demonstrated significant improvement in overall survival (OS) and progression-free survival (PFS) with TAS-102 versus placebo [hazard ratio (HR) = 0.68 and 0.48 for OS and PFS, respectively; both P < 0.001]. The current analysis evaluates efficacy and safety of TAS-102 in the RECOURSE Spanish subgroup.
How we treat metastatic colorectal cancer.
2020
Colorectal cancer is the second leading cause of cancer-related death worldwide. About 20% of patients suffer from metastatic disease at diagnosis, while about one-third of patients treated with curative intent relapsed. In these patients, an accurate staging allows to plan a treatment strategy within a multidisciplinary team in order to achieve predefined goals. Patient's clinical features, tumour characteristics and molecular profile (RAS/BRAF and microsatellite instability (MSI) status) should be considered during the treatment choice. Combination of chemotherapy (fluoropyrimidines, oxaliplatin and irinotecan) plus biological agents (antiepidermal growth factor receptor or antiangiogenic…
Prognostic Value of Sarcopenia in Metastatic Colorectal Cancer Patients Treated with Trifluridine/Tipiracil
2021
Sarcopenia is common in metastatic colorectal cancer (mCRC), increases the risk of treatment-related toxicity and reduces survival. Trifluridine/tipiracil (TT) chemotherapy significantly improved survival in refractory mCRC patients, but the prognostic and predictive role of pretherapeutic sarcopenia and variation in the skeletal muscle index (SMI) during this treatment has not been investigated so far. In this retrospective, observational study, clinical data on mCRC patients treated with TT at six cancer centres in Poland were collected. Computed tomography (CT) scans acquired at the time of initiation of TT (CT1) and on the first restaging (CT2), were evaluated. SMI was assessed based on…