Results of multicenter double-blind placebo-controlled phase II clinical trial of Panagen preparation to evaluate its leukostimulatory activity and formation of the adaptive immune response in patients with stage II-IV breast cancer

Abstract

BackgroundWe performed a multicenter, double-blind, placebo-controlled, phase II clinical trial of human dsDNA-based preparation Panagen in a tablet form. In total, 80 female patients with stage II-IV breast cancer were recruited.MethodsPatients received three consecutive FAC (5-fluorouracil, doxorubicin and cyclophosphamide) or AC (doxorubicin and cyclophosphamide) adjuvant chemotherapies (3 weeks per course) and 6 tablets of 5 mg Panagen or placebo daily (one tablet every 2–3 hours, 30 mg/day) for 18 days during each chemotherapy course. Statistical analysis was performed using Statistica 6.0 software, and non-parametric analyses, namely Wilcoxon-Mann–Whitney and paired Wilcoxon tests. To describe the results, the following parameters were used: number of observations (n), median, interquartile range, and minimum-maximum range.ResultsPanagen displayed pronounced leukostimulatory and leukoprotective effects when combined with chemotherapy. In an ancillary protocol, anticancer effects of a tablet form of Panagen were analyzed. We show that Panagen helps maintain the pre-therapeutic activity level of innate antitumor immunity and induces formation of a peripheral pool of cytotoxic CD8+ perforin + T-cells. Our 3-year follow-up analysis demonstrates that 24% of patients who received Panagen relapsed or died after the therapy, as compared to 45% in the placebo cohort.ConclusionsThe data collected in this trial set Panagen as a multi-faceted “all-in-one” medicine that is capable of simultaneously sustaining hematopoiesis, sparing the innate immune cells from adverse effects of three consecutive rounds of chemotherapy and boosting individual adaptive immunity. Its unique feature is that it is delivered via gastrointestinal tract and acts through the lymphoid system of intestinal mucosa. Taken together, maintenance of the initial levels of innate immunity, development of adaptive cytotoxic immune response and significantly reduced incidence of relapses 3 years after the therapy argue for the anticancer activity of Panagen.Trial registrationClinicalTrials.gov NCT02115984 from 04/07/2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1142-z) contains supplementary material, which is available to authorized users.

Feature of Experimental Breast Cancer Induced by Intermammary Administration of N-Methyl-N-Nitrosourea in Wistar Rat

“…The obtained changes in quantity and quality of cells are as a result of toxic effect of chemotherapeutic agents. During chemotherapy often administered leukostimulatory drugs include of drugs on nucleic acids basis, such as ridostin, derinat, polydan [21]. Panagen belongs to drugs that are based on CpGmodified DNA oligonucleotides and often used for induced anticancer immune response [21].…”

“…During chemotherapy often administered leukostimulatory drugs include of drugs on nucleic acids basis, such as ridostin, derinat, polydan [21]. Panagen belongs to drugs that are based on CpGmodified DNA oligonucleotides and often used for induced anticancer immune response [21]. So, multicenter, double-blind, placebo-controlled, phase II clinical trial of Panagen in female patients with stage II-IV breast cancer displayed leukostimulatory and leukoprotective effects during chemotherapy [21].…”

“…Panagen belongs to drugs that are based on CpGmodified DNA oligonucleotides and often used for induced anticancer immune response [21]. So, multicenter, double-blind, placebo-controlled, phase II clinical trial of Panagen in female patients with stage II-IV breast cancer displayed leukostimulatory and leukoprotective effects during chemotherapy [21]. The development and progression of breast cancer in human are under sex hormones control [8,10,22].…”

Erratum to: Results of multicenter double-blind placebo-controlled phase II clinical trial of Panagen preparation to evaluate its leukostimulatory activity and formation of the adaptive immune response in patients with stage II-IV breast cancer

“…After publication of this work [ 1 ], we noted that we inadvertently failed to include the complete list of all co-authors. In this erratum we rectify these mistakes.…”

Expression of genes of cytokines, transcription factors and differentiation antigens in human dendritic cells activated by double-stranded DNA

“…Было показано также, что препарат двуцепочечной ДНК человека стимулирует продукцию целого ряда цитокинов и хемокинов монону-клеарными клетками цельной крови: ИЛ-1β, ИЛ-6, ИЛ-8, ФНО-α, ИФН-α, ИФН-γ, MCP1, VEGF, ИЛ-1РА и ИЛ-10 ( Orishchenko et al, 2013). Иммуностимулирующая актив-ность двуцепочечной ДНК, в частности в отношении ДК, во многом определяет и обнаруженную нами клиническую эффективность препарата ДНК человека (Панаген ® ) при проведении второй фазы многоцентровых, двойных сле-пых, плацебо-контролируемых испытаний у пациенток с раком молочной железы II-IV стадии (Proskurina et al, 2015(Proskurina et al, , 2016.…”