New Therapeutic Approaches for Tumors With RAS Gene Mutations
There is a huge variety of nucleotide substitutions that activate RAS. The search for new universal drugs for the RAS pathway that either interfere with RAS upregulation upstream in the signaling pathway or offset the consequences of RAS activation is important for improving therapeutic outcomes for patients with refractory malignancies. The use of leflunomide or the combination of MEK inhibitor + hydroxychloroquine ± bevacizumab is promising for patients with mutations in RAS cascade genes who have failed all existing treatment standards.
• Patient is able to provide informed consent and sign approved consent forms to participate in the study.
• Patient age is at least 18 years old.
• Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
• Histologically confirmed metastatic metastatic disease stage 4.
• Must have documented RAS (KRAS, HRAS, NRAS) mutation identified within the last 5 years by a local test on tumor tissue.
• More than 2 lines of standard drug antitumor therapy in the anamnesis.
• Must have disease progression as defined by RECIST version 1.1 criteria
• Appropriate hematologic and liver function:
‣ Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (1500/μL)
⁃ Lymphocyte count ≥ 0.5 x 109/L (500/μL)
⁃ Platelet count ≥ 100 x 109/L (100,000/μL) without transfusion
⁃ Hemoglobin ≥ 90 g/L without transfusion.
⁃ Creatinine clearance ≥ 40 mL/min
⁃ Serum albumin ≥ 25 g/L (2.5 g/dL)
⁃ Serum bilirubin ≤ 1.5 x HGH, with the following exception:
⁃ Patients with known Gilbert's disease or liver metastases: serum bilirubin level ≤ 3 x IUH
⁃ AST, ALT, and alkaline phosphate ≤ 2.5 x HGN;
∙ 10\. For women of childbearing potential: consent to abstinence (abstain from heterosexual intercourse) or use at least two forms of effective contraception with an ineffectiveness rate \< 1% per year during treatment.
∙ 11\. Patients with asymptomatic new or advanced brain metastases (active brain metastases) are eligible to participate if the treating physician determines that localized treatment is not required.