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oai:recercat.cat:11351/73842025-02-08T03:07:23Zcom_2072_378070com_2072_378040col_2072_378092

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study Bordonaro, R. Calvo, A. Auriemma, A. Rubovszky, G. Saunders, M. P. Argilés Martinez, Guillem Tabernero Caturla, Josep Hollebecque, Antoine Institut Català de la Salut [Bordonaro R] Azienda Ospedaliera ARNAS Garibaldi, Catania, Italy. [Calvo A] Gregorio Marañon University General Hospital, Madrid, Spain. [Auriemma A] Azienda Ospedaliera Universitaria Integrat, University of Verona, Verona, Italy. [Hollebecque A] Drug Development Department, Gustave Roussy Cancer Campus, Villejuif, France. [Rubovszky G] Department of Medical Oncology and Clinical Pharmacology, National Institute of Oncology Hungary, Budapest, Hungary. [Saunders MP] Christie NHS Foundation Trust, Manchester, UK. [Argilés G] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Tabernero J] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. UVic-UCC, IOB-Quiron, Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Còlon - Càncer - Tractament Recte - Càncer - Tractament Quimioteràpia combinada DISEASES::Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Gastrointestinal Neoplasms::Intestinal Neoplasms::Colorectal Neoplasms Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols Other subheadings::Other subheadings::Other subheadings::/adverse effects ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias gastrointestinales::neoplasias intestinales::neoplasias colorrectales Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada Otros calificadores::Otros calificadores::Otros calificadores::/efectos adversos Càncer colorectal metastàtic; Oxaliplatina; Trifluridina/Tipiracil Cáncer colorrectal metastásico; Oxaliplatino; Trifluridina/Tipiracil Metastatic colorectal cancer; Oxaliplatin; Trifluridine/tipiracil Background In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment. Patients and methods In 14-day cycles, patients received FTD/TPI 35 mg/m2 (twice daily, days 1-5) plus oxaliplatin 85 mg/m2 (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B). Patients in Cohort B had confirmed MSS status. Results In total, 54 patients were enrolled: 37 in cohort A and 17 in cohort B. Recruitment in cohort B was stopped early due to the low response rate (RR) observed at interim analyses of efficacy. The most common adverse events (AEs) in cohort A were neutropenia/decreased neutrophils (75.7%), nausea (59.5%), vomiting (40.5%), diarrhoea (37.8%), peripheral sensory neuropathy (37.8%), fatigue (35.1%) and decreased appetite (35.1%). In cohort B, the most common AEs were neutropenia/decreased neutrophils (70.6%), diarrhoea (58.8%), nausea (47.1%), vomiting (47.1%), fatigue (47.1%), asthenia (41.2%), paraesthesia (41.2%), thrombocytopenia/decreased platelets (35.3%) and decreased appetite (35.3%). Confirmed objective RR was 17.1% in cohort A and 7.1% in cohort B; the corresponding values for median progression-free survival in the two cohorts were 6.3 and 6.0 months. Conclusion FTD/TPI plus oxaliplatin and bevacizumab or nivolumab had an acceptable safety profile and demonstrated antitumour activity in previously treated patients with mCRC. The study was funded jointly by Servier, France and Taiho Pharmaceutical, Japan. 2022-04-22T13:36:20Z 2022-04-22T13:36:20Z 2021-10 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bordonaro R, Calvo A, Auriemma A, Hollebecque A, Rubovszky G, Saunders MP, et al. Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study. ESMO Open. 2021 Oct 1;6(5):100270. 2059-7029 https://hdl.handle.net/11351/7384 10.1016/j.esmoop.2021.100270 34547581 000704803800020 eng ESMO Open;6(5) https://doi.org/10.1016/j.esmoop.2021.100270 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf Elsevier Scientia