| Added by | llasorsa |
|---|---|
| Group name | EquipeMY |
| Item Type | Journal Article |
| Title | Regorafenib plus FOLFIRINOX as first-line treatment for patients with RAS-mutant metastatic colorectal cancer (FOLFIRINOX-R trial): a dose-escalation study |
| Creator | Adenis et al. |
| Author | Antoine Adenis |
| Author | François Ghiringhelli |
| Author | Ludovic Gauthier |
| Author | Thibault Mazard |
| Author | Ludovic Evesque |
| Author | Alexandre Evrard |
| Author | Patrick Chalbos |
| Author | Aurore Moussion |
| Author | Sophie Gourgou |
| Author | Marc Ychou |
| Abstract | PURPOSE: The combination of bevacizumab and FOLFIRINOX is used in patients with RAS-mutant metastatic colorectal cancer (RASm-mCRC). Regorafenib, an oral multi-tyrosine kinase inhibitor, has antiangiogenic properties, cytostatic effects and also true cytotoxic effects, unlike bevacizumab. The aim of this study was to determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of the regorafenib-FOLFIRINOX combination in patients with RASm-mCRC. METHODS: The FOLFIRINOX-R trial was a phase 1/2 study where the dose-escalation part (3?+?3 design with three dose levels, DLs) was completed before its early termination. FOLFIRINOX (14-day cycle) included oxaliplatin (standard dose), folinic acid, fluorouracil and irinotecan (150 or 180 mg/m²). Regorafenib (120 or 160 mg daily) was given from day 4 to day 10 of each cycle. Dose-limiting toxicity (DLT) was studied in the first three cycles. Eligibility criteria included ECOG performance status???1 and not previously treated RASm-mCRC. RESULTS: Thirteen patients (median age: 65 years; min-max: 40-76) were enrolled. DLT could not be evaluated in one patient (DL3) due to poor observance. The median treatment duration and median follow-up were 6.2 (min-max: 2.3-10) and 13.4 (min-max: 3.8-18.0) months, respectively. Dose was modified in 12/13 (92%) patients. One grade 3 hypokalemia occurred at DL2. MTD was not reached at DL3. Grade 3 diarrhea was recorded in 7/13 patients (13 events) equally distributed in all DLs. CONCLUSION: The RP2D for this regorafenib-FFX combination could not be determined due to a high prevalence of grade 3 diarrhea related to treatment as advised by our Independent Data Monitoring Committee. TRIAL REGISTRATION NUMBERS: ClinicalTrials.gov : NCT03828799. |
| Publication | Cancer Chemotherapy and Pharmacology |
| Volume | 94 |
| Issue | 3 |
| Pages | 443-452 |
| Date | 2024-09 |
| Journal Abbr | Cancer Chemother Pharmacol |
| Language | eng |
| DOI | 10.1007/s00280-024-04682-4 |
| ISSN | 1432-0843 |
| Short Title | Regorafenib plus FOLFIRINOX as first-line treatment for patients with RAS-mutant metastatic colorectal cancer (FOLFIRINOX-R trial) |
| Library Catalog | PubMed |
| Extra | PMID: 38987363 PMCID: PMC11420384 |
| Tags | Adult, Aged, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms, Dose-Response Relationship, Drug, Female, Fluorouracil, FOLFIRINOX, Humans, Leucovorin, Male, Maximum Tolerated Dose, Middle Aged, Mutation, Neoplasm Metastasis, Phase 1 trial, Phenylurea Compounds, Pyridines, Recommended phase 2 dose, Regorafenib |
| Date Added | 2024/10/10 - 16:17:05 |
| Date Modified | 2024/10/10 - 16:17:05 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
