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- Title
Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study.
- Authors
Taniguchi, Hiroya; Yamazaki, Kentaro; Masuishi, Toshiki; Kawakami, Takeshi; Onozawa, Yusuke; Honda, Kazunori; Kadowaki, Shigenori; Narita, Yukiya; Tsushima, Takahiro; Hamauchi, Satoshi; Todaka, Akiko; Yokota, Tomoya; Ando, Masashi; Mori, Keita; Shirasu, Hiromichi; Yasui, Hirofumi; Muro, Kei
- Abstract
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: 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: 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: 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)]. In this phase Ib study, MODURATE, efficacy and safety of trifluridine/tipiracil, irinotecan, and bevacizumab was tested in patients with metastatic colorectal cancer with fluoropyrimidine and oxaliplatin treatment failure
- Subjects
DRUG efficacy; EXPERIMENTAL design; CLINICAL trials; DRUG dosage; DEOXYRIBONUCLEOSIDES; CANCER chemotherapy; IRINOTECAN; METASTASIS; ANTINEOPLASTIC agents; NEUTROPENIA; COLORECTAL cancer; CANCER patients; TREATMENT delay (Medicine); RESEARCH funding; DRUG therapy; DESCRIPTIVE statistics; BEVACIZUMAB; TERMINATION of treatment; PROGRESSION-free survival; PATIENT safety; LONGITUDINAL method; DRUG toxicity; OVERALL survival; EVALUATION
- Publication
Oncologist, 2023, Vol 28, Issue 11, pe1108
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1093/oncolo/oyad143