Regorafenib plus FOLFIRINOX as first-line treatment for patients with RAS-mutant metastatic colorectal cancer (FOLFIRINOX-R trial): a dose-escalation study

被引：1

作者：

Adenis, Antoine ^{[1
]}

Ghiringhelli, Francois ^{[2
]}

Gauthier, Ludovic ^{[3
]}

Mazard, Thibault ^{[1
]}

Evesque, Ludovic ^{[4
]}

Evrard, Alexandre ^{[5
,6
]}

Chalbos, Patrick ^{[7
]}

Moussion, Aurore ^{[7
]}

Gourgou, Sophie ^{[3
]}

Ychou, Marc ^{[1
]}

机构：

[1] Montpellier Univ, Montpellier Canc Inst ICM, Med Oncol Dept, INSERM,U1194, F-34298 Montpellier, France

[2] Ctr Georges Francois Leclerc, Med Oncol Dept, Dijon, France

[3] Montpellier Univ, Montpellier Canc Inst ICM, Biometr Unit, Montpellier, France

[4] Ctr Antoine Lacassagne, Med Oncol Dept, Nice, France

[5] Montpellier Univ, Montpellier Canc Res Inst IRCM, INSERM, U1194, Montpellier, France

[6] Univ Montpellier, Nimes Univ Hosp, Lab Biochem & Mol Biol, INSERM,IRCM, Montpellier, France

[7] Montpellier Univ, Montpellier Canc Inst ICM, Clin Res & Innovat Dept, Montpellier, France

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2024年 / 94卷 / 03期

关键词：

Regorafenib; FOLFIRINOX; Colorectal cancer; Phase; 1; trial; Recommended phase 2 dose; BAY; 73-4506; PHASE-II; IRINOTECAN; FOLFOXIRI; POLYMORPHISMS; MULTICENTER; BEVACIZUMAB; GEMCITABINE; OXALIPLATIN; TOXICITY;

D O I：

10.1007/s00280-024-04682-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposeThe 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.MethodsThe 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/m(2)). 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.ResultsThirteen 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.ConclusionThe 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 numbersClinicalTrials.gov: NCT03828799.

引用

页码：443 / 452

页数：10

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