Bevacizumab, Irinotecan, and Biweekly Trifluridine/Tipiracil for Metastatic Colorectal Cancer: MODURATE, a Phase Ib Study.
| Autor: | 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 |
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| Předmět: |
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 |
| Zdroj: | Oncologist; Nov2023, Vol. 28 Issue 11, pe1108-e1113, 6p |
| Abstrakt: | 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 [ABSTRACT FROM AUTHOR] |
| Databáze: | Complementary Index |
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