Immunosurveillance for Metastatic Colorectal Cancer

The Role of Neutrophil Mitochondrial Dysfunction in Medical Rehabilitation During Palliative Chemotherapy for Metastatic Colorectal Cancer

The goal of this clinical trial is to learn if adding sodium nucleinate to FOLFOX chemotherapy helps people with metastatic colorectal cancer (colon or rectal cancer that has spread). Researchers will also look at side effects and how people feel during treatment.

The main questions this study aims to answer are:

1. Does adding sodium nucleinate help treatment work better?
2. Does it improve quality of life (how people feel and function day to day)?
3. Does it affect survival at one year?

Researchers will compare:

1. FOLFOX chemotherapy plus sodium nucleinate versus
2. FOLFOX chemotherapy alone

Participants will:

1. Be randomly assigned (like flipping a coin) to one of the two groups;
2. Receive four cycles of FOLFOX chemotherapy;
3. Take sodium nucleinate daily if assigned to that group;
4. Have checkups and blood tests during the study (including tumor marker blood tests such as CEA and CA 19-9);
5. Complete quality-of-life questionnaires and have other planned tests that look at immune cells and how certain blood cells work;
6. Be followed after treatment to see how they are doing, including up to one year after starting the study.

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.

Inclusion Criteria:

1. Histologically confirmed colorectal cancer.
2. Locally advanced or metastatic disease as treated with palliative FOLFOX per protocol (including metastatic disease [M1]).
3. Able to receive FOLFOX chemotherapy and to comply with study procedures.
4. Provided written informed consent.

Exclusion Criteria:

1. Active pulmonary tuberculosis.
2. Decompensated diabetes mellitus.
3. Decompensated cardiac, vascular, pulmonary, hepatic, or renal failure.