Prophylaxis of Hematologic Complications With Naderin in First-Line Breast Cancer Chemotherapy

Study Rationale Myelosuppression and related immunologic complications are common dose-limiting toxicities of cytotoxic chemotherapy and can lead to treatment delays, dose reductions, or discontinuation. This study assessed prophylactic administration of Naderin (sodium deoxyribonucleate; immunomodulatory agent) as supportive care during first-line AC chemotherapy, with the intent to mitigate hematologic toxicity and preserve chemotherapy delivery.

Study Design and Setting This was a prospective, open-label, two-group interventional study conducted at the Kazakh Scientific Research Institute of Oncology and Radiology (Almaty, Kazakhstan) in collaboration with KazNMU and the Almaty Oncology Center. Treatment allocation was non-randomized and based on consecutive enrollment, treatment availability, and participant consent.

Study Groups and Interventions Control group: standard institutional AC chemotherapy (doxorubicin + cyclophosphamide), intravenous administration, 4 planned cycles.

Intervention group: the same AC chemotherapy regimen plus Naderin administered as a prophylactic adjunct with each chemotherapy cycle (route and dosing per local institutional protocol).

Concomitant medications and supportive care (including any antiemetics, antimicrobials, or use of colony-stimulating factors) were permitted according to institutional practice and recorded.

Assessments and Follow-up

Participants underwent:

Baseline evaluation prior to chemotherapy initiation, including clinical assessment and laboratory testing.

On-treatment monitoring during each AC cycle with serial complete blood counts and structured adverse-event assessment.

End-of-treatment evaluation after completion of planned chemotherapy cycles (or earlier discontinuation), including laboratory reassessment and documentation of chemotherapy delivery (cycle completion, delays, interruptions).

Outcomes (high-level; details recorded elsewhere) The study evaluated hematologic toxicity during chemotherapy and chemotherapy delivery feasibility (ability to complete planned cycles without interruption), along with safety/tolerability of adjunctive Naderin.

Statistical Approach (high-level) The primary between-group comparison for hematologic toxicity incidence was planned using categorical testing (chi-square) with a two-sided alpha threshold of 0.05, with descriptive summaries of chemotherapy delivery metrics and adverse events.

Ethical and Oversight Considerations The study was approved by the Local Ethics Committee of KazNMU (Approval No. 15677). Written informed consent was obtained from all participants prior to enrollment. No independent data monitoring committee was used.

• Naderin (Drug), also known as Sodium Deoxyribonucleate, Sodium nucleinate: Naderin is an immunomodulatory agent containing sodium deoxyribonucleate. It activates cellular and humoral immunity, stimulates reparative processes, and exhibits anti-inflammatory properties. It is administered locally alongside each chemotherapy cycle as prophylaxis against hematologic and immunologic complications. The agent is rapidly absorbed upon administration, distributed through lymphatic pathways to organs and tissues, and excreted primarily via the kidneys.
• AC Chemotherapy (Drug), also known as Doxorubicin and Cyclophosphamide: Standard first-line chemotherapy regimen consisting of doxorubicin (an anthracycline antibiotic) and cyclophosphamide (an alkylating agent). Administered intravenously for 4 cycles at standard institutional dosing. This is the backbone chemotherapy regimen for both study arms, with the experimental arm receiving Naderin as an adjunct prophylactic agent

Primary outcomes

• Incidence of leukopenia during chemotherapy [Through chemotherapy completion, up to 4 months]: Proportion of participants who develop leukopenia (white blood cell count below the institutional lower limit of normal) during any of the 4 chemotherapy cycles. Leukopenia is defined as a decrease in circulating white blood cells below 4.0 × 10⁹/L (or per institutional laboratory reference range)

Secondary outcomes

• Chemotherapy completion rate [At the end of treatment, up to 4 months]: Proportion of participants who successfully complete all 4 planned cycles of AC chemotherapy without interruption, dose reduction, or premature discontinuation.
• Rate of chemotherapy interruption [Through chemotherapy completion, up to 4 months]: Proportion of participants requiring chemotherapy interruption, dose delay, or premature discontinuation due to hematologic complications or other adverse events.
• Requirement for colony-stimulating factors [Through chemotherapy completion, up to 4 months]: Proportion of participants requiring administration of granulocyte colony-stimulating factors (G-CSF) for management of chemotherapy-induced neutropenia.
• Quality of Life assessment [Baseline and at end of treatment, up to 4 months]: Change from baseline to end of chemotherapy in Global Health Status/Quality of Life (GHS/QoL) using EORTC QLQ-C30 (version 3.0). Scores are transformed to a 0-100 scale; higher scores indicate better QoL for GHS/QoL and functioning scales (and worse symptoms for symptom scales-if reported).
• All-cause mortality [Through study completion, up to 12 months]: Proportion of participants who died from any cause during the study period.

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Confirmed histological diagnosis of breast cancer
* Receiving first-line AC chemotherapy (doxorubicin + cyclophosphamide)
* Age 18 years or older
* Female sex
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2
* Adequate bone marrow function (absolute neutrophil count ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L)
* Adequate hepatic function (transaminases ≤ 2.5 × upper limit of normal)
* Adequate renal function (creatinine ≤ 1.5 × upper limit of normal)
* Normal cardiac function (left ventricular ejection fraction ≥ 50%)
* Willing and able to provide written informed consent

Exclusion Criteria:

* Previous chemotherapy or radiotherapy for breast cancer
* History of other malignant neoplasms (except non-melanoma skin cancer or carcinoma in situ of the cervix)
* Severe organ dysfunction (cardiac, hepatic, renal, pulmonary)
* Active infection requiring systemic therapy
* Known hypersensitivity to Naderin or any of its components
* Known hypersensitivity to doxorubicin, cyclophosphamide, or any excipients
* Pregnancy or breastfeeding
* Psychiatric or cognitive impairment that would interfere with study participation
* Participation in another interventional clinical trial within 30 days prior to enrollment
* Any condition that, in the investigator's opinion, would compromise participant safety or interfere with study objectives