A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer
| العنوان: | A Phase I dose-escalation study of third-line regorafenib with trifluridine/tipiracil in metastatic colorectal cancer |
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| المؤلفون: | Alexander Stein, Maurice Michel, Jens U. Marquardt, Helge Schroeder, Oliver Waidmann, Marcus-Alexander Woerns, Arndt Weinmann, Markus Moehler, Martin Maenz, Joseph Tintelnot, Friedrich Foerster, Joerg Trojan |
| المصدر: | Future Oncology. 17:3309-3319 |
| بيانات النشر: | Future Medicine Ltd, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Pyrrolidines, Maximum Tolerated Dose, Pyridines, Colorectal cancer, Administration, Oral, Trifluridine, Drug Administration Schedule, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Refractory, Regorafenib, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Dose escalation, Humans, Response Evaluation Criteria in Solid Tumors, Aged, Tipiracil, Dose-Response Relationship, Drug, business.industry, Phenylurea Compounds, General Medicine, Middle Aged, medicine.disease, Progression-Free Survival, Drug Combinations, 030104 developmental biology, chemistry, Third line, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Hypertension, Toxicity, Feasibility Studies, Female, Colorectal Neoplasms, business, Thymine, medicine.drug |
| الوصف: | 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. |
| تدمد: | 1744-8301 1479-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d2cde2e1bcd22c3bd2bdf2e561d4671 https://doi.org/10.2217/fon-2021-0278 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1d2cde2e1bcd22c3bd2bdf2e561d4671 |
| قاعدة البيانات: | OpenAIRE |
PDF full text from Publisher | تدمد: | 17448301 14796694 |
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