A Phase i dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

Markus Moehler; Maurice Michel; Alexander Stein; Joerg Trojan; Jens Marquardt; Joseph Tintelnot; Oliver Waidmann; Arndt Weinmann; Marcus Alexander Woerns; Helge Schroeder; Martin Maenz; Friedrich Foerster

doi:10.2217/fon-2021-0278

A Phase i dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

Markus Moehler^*, Maurice Michel, Alexander Stein, Joerg Trojan, Jens Marquardt, Joseph Tintelnot, Oliver Waidmann, Arndt Weinmann, Marcus Alexander Woerns, Helge Schroeder, Martin Maenz, Friedrich Foerster

^*Korrespondierende/r Autor/-in für diese Arbeit

Medizinische Klinik I

5 Zitate (Scopus)

Abstract

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 is FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d. Median progression-free survival was 3.81 months (95% CI: 1.51-5.29), median OS 11.1 months (95% CI: 2.3-18.2). Conclusion: The combination of REG and FTD/TPI is feasible and safe. Efficacy signals exceed that of the single agents at acceptable toxicity levels and are clinically meaningful.

Originalsprache	Englisch
Zeitschrift	Future Oncology
Jahrgang	17
Ausgabenummer	25
Seiten (von - bis)	3309-3319
Seitenumfang	11
ISSN	1479-6694
DOIs	https://doi.org/10.2217/fon-2021-0278
Publikationsstatus	Veröffentlicht - 09.2021

Fördermittel

The study was supported by a grant from B Vital GmbH. M Michel was supported by the Clinician Scientist Fellowship ‘Else Kröner Research College: 2018 Kolleg.05’. M Moehler reports a scientific grant from Bayer for his institution personal fees, as well honoraria and travel support by Bayer, Taiho and Servier. A Stein received institutional research funding and honoraria for advisory boards or lectures from Servier. J Trojan received honoraria for talks and advisory board role from Bayer and Servier. J Marquardt received honoraria and/or travel expenses from Bayer. O Waidmann received honoraria for advisory boards from Servier and Bayer, and honoraria for lectures from Bayer. M-A Woerns received honoraria and/or travel expenses from Bayer. F Foerster collaborates with Bayer in scientific pursuits. M Michel, J Tintelnot, A Weinmann, H Schroeder and M Maenz declare no conflict of interest.The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

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title = "A Phase i dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer",

abstract = "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 is FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d. Median progression-free survival was 3.81 months (95\% CI: 1.51-5.29), median OS 11.1 months (95\% CI: 2.3-18.2). Conclusion: The combination of REG and FTD/TPI is feasible and safe. Efficacy signals exceed that of the single agents at acceptable toxicity levels and are clinically meaningful.",

author = "Markus Moehler and Maurice Michel and Alexander Stein and Joerg Trojan and Jens Marquardt and Joseph Tintelnot and Oliver Waidmann and Arndt Weinmann and Woerns, \{Marcus Alexander\} and Helge Schroeder and Martin Maenz and Friedrich Foerster",

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T1 - A Phase i dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

AU - Moehler, Markus

AU - Michel, Maurice

AU - Stein, Alexander

AU - Trojan, Joerg

AU - Marquardt, Jens

AU - Tintelnot, Joseph

AU - Waidmann, Oliver

AU - Weinmann, Arndt

AU - Woerns, Marcus Alexander

AU - Schroeder, Helge

AU - Maenz, Martin

AU - Foerster, Friedrich

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N2 - 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 is FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d. Median progression-free survival was 3.81 months (95% CI: 1.51-5.29), median OS 11.1 months (95% CI: 2.3-18.2). Conclusion: The combination of REG and FTD/TPI is feasible and safe. Efficacy signals exceed that of the single agents at acceptable toxicity levels and are clinically meaningful.

AB - 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 is FTD/TPI 25 mg/m2 b.i.d. + REG 120 mg/d. Median progression-free survival was 3.81 months (95% CI: 1.51-5.29), median OS 11.1 months (95% CI: 2.3-18.2). Conclusion: The combination of REG and FTD/TPI is feasible and safe. Efficacy signals exceed that of the single agents at acceptable toxicity levels and are clinically meaningful.

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A Phase i dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer

Abstract

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