Clin Cancer Research: Qumetinib Joint 5-FU CRT For Advanced Rectal Cancer

BACKGROUND: The RAS/RAF/MEK/ERK signaling pathway is critical to the development ofcolorectal cancer, and KRAS, NRAS, and BRAF mutations drive tumor tolerance to radiation therapyThis study is a Phase I clinical trial designed to assess the safety of the MEK1/2 inhibitor trametinib (qumetinib) in combination with 5-fluorourener (5-FU) chemotherapy (CRT) for localized advanced rectal cancer (LARC)method: This study adopted a 3-3 design to recruit patients with rectal cancer ii/IIIAfter 5 days of curmetinib introduction and a biopsy of a tumor before and after treatment, the patient underwent qumetinib and CRT, surgery and complementary chemotherapyQumetiniby regimen: 0.5 mg, 1 mg or 2 mg orally, 1/dayCRT contains 5-FU 225 mg/m2/day, radiotherapy 1.8Gy/day (total dose 50.4 Gy)The main node is the clear MTD and the recommended Phase II trial doseresults: the subjects were divided into different dose levels of treatment groups, and 18 patients were able to participate in toxicity and reactive assessmentTreatment is well tolerated, with only one case of dose-restricted toxicity (diarrhea) occurring, mainly mainly because of CRT rather than qumetidinibAt the 2 mg dose level, 25% of patients received a complete remission of the diseaseIHC staining confirmed a dose-dependent decrease in pERK as the dose of qumerinib increasedconclusion: The joint scheme of Qumetinib and 5-FU CRT is safe and well tolerated for rectal cancer and requires further validation of Phase II trials