Immunosurveillance for Metastatic Colorectal Cancer

This randomized, single-blinded, parallel-group clinical trial was approved by the Local Ethics Committee of Kazakh National Medical University and conducted at oncology centers affiliated with university clinics in four regions of Kazakhstan. Participants had histologically confirmed metastatic colorectal cancer (T3-4 N1-2 M1). A total of 200 individuals were screened; 187 were enrolled and randomized. Participants were allocated in a 1:1 ratio using sealed envelopes to receive either (1) FOLFOX chemotherapy plus sodium nucleinate or (2) FOLFOX chemotherapy alone. The intervention group received sodium nucleinate 50 mg per day (25 mg in the morning and 25 mg at lunch), starting 1 week before the first chemotherapy cycle and continued daily for 4 months. Both groups received four cycles of FOLFOX per institutional protocols. Assessments included monthly clinical evaluation with general and biochemical blood tests during treatment. The following were assessed at baseline and at 1 month after completion of chemotherapy (approximately 5 months after baseline): FDG PET/CT, serum tumor markers (CEA and CA 19-9), peripheral blood immunologic status (CD4+/CD8+ ratio), and neutrophil mitochondrial activity (percentage of neutrophils with preserved mitochondrial function among 200 counted neutrophils). Baseline transthoracic echocardiography was performed to determine left ventricular ejection fraction. Health-related quality of life was assessed using the EORTC QLQ-C30 at baseline, post-treatment, and 1 year post-baseline. Analyses were performed using Statistica 7.0 (StatSoft, USA). Continuous outcomes were compared between groups using the Mann-Whitney U test as specified in the protocol.