Results of the feasibility study of clinical trials of the new cancer treatment technology Karanahan for patients with advanced breast cancer.

Background: Multi-year research into the synergistic effect of cyclophosphamide (CP) and complex composite double-stranded DNA preparation (DNAmix) has made it possible to develop the novel Karanahan technology for treating malignant tumors. After being applied, the technology results in eradication of cancer stem cells, induction of extensive apoptosis of committed cancer cells, and destruction of suppressor activity of tumor-associated stroma. The therapeutic efficacy of the Karanahan cancer treatment technology is independent of both tumor immunogenicity and the patient's immune status. Breast cancer is the most common human malignancy; its treatment remains extremely challenging in current clinical practice. It is suggested that in patients with advanced breast cancer, the Karanahan technology will ensure therapeutic eradication of cancer stem cells, substantially slowing down disease progression and extending the survival of palliative patients. The objective of this clinical trial is to examine the feasibility and practical applicability of the Karanahan technology in clinical practice for patients with advanced breast cancer and identify critical elements of the technology when transferred from animal models to humans. Methods: Clinical trials of feasibility of the Karanahan technology were conducted in patients with advanced stage IV breast cancer and palliative status. Patients were enrolled consecutively based on the decision of a local case conference. The officially registered trial protocol contained all the requisite provisions, involving the inclusion/non-inclusion criteria, conditions of therapeutic intervention, informed consent, and study endpoints. Results: According to the key characteristics of the Karanahan technology, the therapeutic success is independent of the molecular subtype of breast cancer. Presence of cancer stem cells in the tumor was shown to be important for all the subtypes of the disease. The findings indicate that the analyzed treatment regimen ensures a positive local therapeutic response. Partial tumor response to the Karanahan cancer treatment technology or disease stabilization was observed in eight patients. Karanahan treatment activates the adaptive antitumor immune response in 78% of patients. The median survival time of patients significantly increased from 6 months (historical control) to 20 months after Karanahan treatment. The study design was optimized, including the selection of the optimal dose and refinement of the elements of the intervention procedure. The accrual rate for patients meeting the inclusion criteria suggests that randomized large-scale clinical trials should be conducted at the major cancer treatment centers. Conclusions: The results of studying the feasibility and practical applicability of the novel antitumor Karanahan therapy indicate that measures can be prepared for developing a protocol and design for pilot and large-scale clinical trials of this approach. The critical elements of the experimental Karanahan technology for transferring it to clinical practice for treating advanced breast cancer have been identified.