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

^*Corresponding author for this work

Clinic of Internal Medicine I

1 Citation (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.

Original language	English
Journal	Future Oncology
Volume	17
Issue number	25
Pages (from-to)	3309-3319
Number of pages	11
ISSN	1479-6694
DOIs	https://doi.org/10.2217/fon-2021-0278
Publication status	Published - 09.2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.2217/fon-2021-0278

Cite this

@article{603d0f61b0014fc8a586782c3d32dc44,

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",

note = "Publisher Copyright: {\textcopyright} 2021 AIO-Studien-gGmbH.",

year = "2021",

month = sep,

doi = "10.2217/fon-2021-0278",

language = "English",

volume = "17",

pages = "3309--3319",

journal = "Future Oncology",

issn = "1479-6694",

number = "25",

}

TY - JOUR

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

PY - 2021/9

Y1 - 2021/9

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.

UR - http://www.scopus.com/inward/record.url?scp=85113364589&partnerID=8YFLogxK

U2 - 10.2217/fon-2021-0278

DO - 10.2217/fon-2021-0278

M3 - Journal articles

C2 - 33993741

AN - SCOPUS:85113364589

SN - 1479-6694

VL - 17

SP - 3309

EP - 3319

JO - Future Oncology

JF - Future Oncology

IS - 25

ER -

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

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this