EXPLORING THE INTRAVENOUS COMBINATION OF D-ISOASCORBIC ACID (D-VC) AND ARSENIC TRIOXIDE IN ADVANCED/METASTATIC MALIGNANCIES

Background: Addressing the therapeutic challenges associated with Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutant cancers remains a significant focus in oncology. The combined intravenous administration of the D-isomer of vitamin C (D-VC) (dextro-rotatory isomer of ascorbic acid) and arsenic trioxide (ATO) is proposed as a potential approach for achieving an anti-tumor effect in Colorectal cancer (CRC) with KRAS-mutant tumor cells. ATO enhances the oxidative effect of vitamin C (VC), and the combination of both drugs provides effective eradication of KRAS-mutant cancer cells. A potent synergistic effect of the VC and ATO combination has been observed about KRAS-mutant cancer cells. Purpose: This clinical trial aims to assess the tolerability and safety of intravenous administration of D-VC along with ATO in patients with advanced/metastatic malignancies who have exhausted standard therapy. Methods and Patients: This single-center Phase I clinical trial evaluated the tolerability and safety of D-VC when administered intravenously alone or in sequential administration with ATO. The target group for the Phase I exploratory clinical trial includes 10 patients with advanced/metastatic malignant neoplasms who have exhausted standard therapy. Results: The administration of the drug followed the treatment regimen according to the ap-proved study protocol. After a single intravenous infusion of D-VC in escalating doses of 0.05 g/kg - 0.1 g/kg - 0.15 g/kg - 0.3 g/kg all patients felt satisfactory, and no subjective intolerance to the investigational drug was reported. The main functional and laboratory parameters remained within normal values recorded at the start of the study. The maximum tolerated dose of D-VC was determined to be 0.3 g/kg, and this dose was chosen as the baseline for the second stage of the study, where D-VC (0.3 g/kg) was administered alongside ATO (0.15 mg/kg). Conclusions: Our findings showed favorable safety and well-tolerated profiles and provided the recommended dose for high-dose D-VC in combination with АТО.