Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study.
bevacizumab
chemotherapy
colorectal cancer
irinotecan
trifluridine/tipiracil
Journal
The oncologist
ISSN: 1549-490X
Titre abrégé: Oncologist
Pays: England
ID NLM: 9607837
Informations de publication
Date de publication:
02 Nov 2023
02 Nov 2023
Historique:
received:
03
01
2023
accepted:
23
04
2023
medline:
8
11
2023
pubmed:
7
6
2023
entrez:
7
6
2023
Statut:
ppublish
Résumé
In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure. We included a dose escalation (3 + 3 design) and an expansion cohort. Patients were administered trifluridine/tipiracil (25-35 mg/m2 twice daily, days 1-5), irinotecan (150-180 mg/m2, day 1), and bevacizumab (5 mg/kg, day 1) every 2 weeks. The recommended phase II dose (RP2D) in the dose escalation cohort was administered to at least 15 patients in both cohorts combined. Twenty-eight patients were enrolled. Five dose-limiting toxicities were observed. RP2D was defined as trifluridine/tipiracil 35 mg/m2, irinotecan 150 mg/m2, and bevacizumab 5 mg/kg. Of 16 patients who received RP2D, 86% (14/16) experienced grade ≥3 neutropenia without febrile neutropenia. Dose reduction, delay, and discontinuation occurred in 94%, 94%, and 6% of patients, respectively. Three patients (19%) showed partial response and 5 had stable disease for >4 months, with a median progression-free and overall survival of 7.1 and 21.7 months, respectively. Biweekly trifluridine/tipiracil, irinotecan, and bevacizumab administration may have moderate antitumor activity with high risk of severe myelotoxicity in previously treated patients with metastatic colorectal cancer [UMIN Clinical Trials Registry (UMIN000019828) and Japan Registry of Clinical Trials (jRCTs041180028)].
Sections du résumé
BACKGROUND
BACKGROUND
In this phase Ib study MODURATE, we optimized the dosing schedule and tested the efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure.
METHODS
METHODS
We included a dose escalation (3 + 3 design) and an expansion cohort. Patients were administered trifluridine/tipiracil (25-35 mg/m2 twice daily, days 1-5), irinotecan (150-180 mg/m2, day 1), and bevacizumab (5 mg/kg, day 1) every 2 weeks. The recommended phase II dose (RP2D) in the dose escalation cohort was administered to at least 15 patients in both cohorts combined.
RESULTS
RESULTS
Twenty-eight patients were enrolled. Five dose-limiting toxicities were observed. RP2D was defined as trifluridine/tipiracil 35 mg/m2, irinotecan 150 mg/m2, and bevacizumab 5 mg/kg. Of 16 patients who received RP2D, 86% (14/16) experienced grade ≥3 neutropenia without febrile neutropenia. Dose reduction, delay, and discontinuation occurred in 94%, 94%, and 6% of patients, respectively. Three patients (19%) showed partial response and 5 had stable disease for >4 months, with a median progression-free and overall survival of 7.1 and 21.7 months, respectively.
CONCLUSION
CONCLUSIONS
Biweekly trifluridine/tipiracil, irinotecan, and bevacizumab administration may have moderate antitumor activity with high risk of severe myelotoxicity in previously treated patients with metastatic colorectal cancer [UMIN Clinical Trials Registry (UMIN000019828) and Japan Registry of Clinical Trials (jRCTs041180028)].
Identifiants
pubmed: 37284901
pii: 7191653
doi: 10.1093/oncolo/oyad143
pmc: PMC10628564
doi:
Substances chimiques
tipiracil
NGO10K751P
Bevacizumab
2S9ZZM9Q9V
Irinotecan
7673326042
Uracil
56HH86ZVCT
Trifluridine
RMW9V5RW38
Drug Combinations
0
Types de publication
Clinical Trial, Phase I
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1108-e1113Subventions
Organisme : Taiho Pharmaceutical
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press.
Références
Anticancer Res. 2015 Mar;35(3):1437-45
pubmed: 25750295
Lancet Oncol. 2015 May;16(5):499-508
pubmed: 25877855
Invest New Drugs. 2015 Oct;33(5):1068-77
pubmed: 26163340
J Clin Oncol. 2012 Oct 1;30(28):3499-506
pubmed: 22949147
Oncol Rep. 2015 May;33(5):2135-42
pubmed: 25812794
Lancet Oncol. 2013 Jan;14(1):29-37
pubmed: 23168366
Cancer Sci. 2011 Oct;102(10):1868-73
pubmed: 21740478
Clin Cancer Res. 2020 Apr 1;26(7):1555-1562
pubmed: 31924737
Oncologist. 2020 Dec;25(12):e1855-e1863
pubmed: 32666647
Br J Cancer. 2023 May;128(10):1897-1905
pubmed: 36871043