title: 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: BACKGROUND
  We 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  Panagen 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.
  
  
  CONCLUSIONS
  The 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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02115984 from 04/07/2014.
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. asproskurina@gmail.com.
authors.forename: Anastasia S
authors.initials: AS
authors.lastname: Proskurina
authors.affiliation: Novosibirsk State Medical University, Novosibirsk, 630091, Russia. ne@spd.name.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Gvozdeva
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. alamkina@gmail.com.
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Alyamkina
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. zhenk123@mail.ru.
authors.forename: Evgenia V
authors.initials: EV
authors.lastname: Dolgova
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. keor@ngs.ru.
authors.forename: Konstantin E
authors.initials: KE
authors.lastname: Orishchenko
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. nikolin@gorodok.net.
authors.forename: Valeriy P
authors.initials: VP
authors.lastname: Nikolin
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. nelly@bionet.nsc.ru.|Novosibirsk State University, Novosibirsk, 630090, Russia. nelly@bionet.nsc.ru.
authors.forename: Nelly A
authors.initials: NA
authors.lastname: Popova
authors.affiliation: Novosibirsk State University, Novosibirsk, 630090, Russia. svsidorov@yandex.ru.|Oncology Department of Municipal Hospital No 1, Novosibirsk, 630047, Russia. svsidorov@yandex.ru.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Sidorov
authors.affiliation: Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630099, Russia. ct_lab@mail.ru.
authors.forename: Elena R
authors.initials: ER
authors.lastname: Chernykh
authors.affiliation: Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630099, Russia. ostanin62@mail.ru.
authors.forename: Alexandr A
authors.initials: AA
authors.lastname: Ostanin
authors.affiliation: Institute of Clinical Immunology, Siberian Branch of the Russian Academy of Medical Sciences, Novosibirsk, 630099, Russia. oleplina@mail.ru.
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Leplina
authors.affiliation: Irkutsk State Medical Academy of Postgraduate Education, Irkutsk, 664049, Russia. vv.dvornichenko@gmail.com.|Regional Oncology Dispensary, Irkutsk, 664035, Russia. vv.dvornichenko@gmail.com.
authors.forename: Victoria V
authors.initials: VV
authors.lastname: Dvornichenko
authors.affiliation: Irkutsk State Medical Academy of Postgraduate Education, Irkutsk, 664049, Russia. ponomarenkodm@gmail.com.|Regional Oncology Dispensary, Irkutsk, 664035, Russia. ponomarenkodm@gmail.com.
authors.forename: Dmitriy M
authors.initials: DM
authors.lastname: Ponomarenko
authors.affiliation: Novosibirsk State University, Novosibirsk, 630090, Russia. sgs@newmail.ru.|Clinic Department of the Central Clinical Hospital, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, 630090, Russia. sgs@newmail.ru.
authors.forename: Galina S
authors.initials: GS
authors.lastname: Soldatova
authors.affiliation: CJSC "Vector-best", Koltsovo, Novosibirsk region, 630559, Russia. varaksin@vector-best.ru.
authors.forename: Nikolay A
authors.initials: NA
authors.lastname: Varaksin
authors.affiliation: CJSC "Vector-best", Koltsovo, Novosibirsk region, 630559, Russia. tatria@mail.ru.
authors.forename: Tatiana G
authors.initials: TG
authors.lastname: Ryabicheva
authors.forename: Peter N
authors.initials: PN
authors.lastname: Uchakin
authors.affiliation: Novosibirsk State University, Novosibirsk, 630090, Russia. snz@post.nsu.ru.
authors.forename: Stanislav N
authors.initials: SN
authors.lastname: Zagrebelniy
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. rogachev@bionet.nsc.ru.
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Rogachev
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia. labmolbiol@mail.ru.
authors.forename: Sergey S
authors.initials: SS
authors.lastname: Bogachev
authors.affiliation: LLC Panagen, Gorno-Altaisk, 649000, Russia. shurdov@gmail.com.
authors.forename: Mikhail A
authors.initials: MA
authors.lastname: Shurdov
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D019891:Leukopoiesis / Q000187:drug effects* / Q000276:immunology
chemical_list: D004247:DNA