泛基因制剂多中心双盲安慰剂对照II期临床试验结果，以评估其对II-IV期乳腺癌患者的白细胞刺激活性和适应性免疫反应的形成。

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.

作者信息

Proskurina Anastasia S, Gvozdeva Tatiana S, Alyamkina Ekaterina A, Dolgova Evgenia V, Orishchenko Konstantin E, Nikolin Valeriy P, Popova Nelly A, Sidorov Sergey V, Chernykh Elena R, Ostanin Alexandr A, Leplina Olga Y, Dvornichenko Victoria V, Ponomarenko Dmitriy M, Soldatova Galina S, Varaksin Nikolay A, Ryabicheva Tatiana G, Uchakin Peter N, Zagrebelniy Stanislav N, Rogachev Vladimir A, Bogachev Sergey S, Shurdov Mikhail A

机构信息

Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, 10 Lavrentieva ave, Novosibirsk, 630090, Russia.

Novosibirsk State Medical University, Novosibirsk, 630091, Russia.

出版信息

BMC Cancer. 2015 Mar 13;15:122. doi: 10.1186/s12885-015-1142-z.

DOI:10.1186/s12885-015-1142-z

PMID:25886605

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4365563/

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.

TRIAL REGISTRATION

ClinicalTrials.gov NCT02115984 from 04/07/2014.

摘要

背景

我们开展了一项多中心、双盲、安慰剂对照的II期临床试验，研究片剂形式的基于人双链DNA的制剂Panagen。总共招募了80名II-IV期乳腺癌女性患者。

方法

患者接受三个连续疗程的FAC（5-氟尿嘧啶、阿霉素和环磷酰胺）或AC（阿霉素和环磷酰胺）辅助化疗（每疗程3周），在每个化疗疗程期间，每天服用6片5毫克的Panagen或安慰剂（每2-3小时1片，30毫克/天），共18天。使用Statistica 6.0软件进行统计分析，采用非参数分析，即Wilcoxon-Mann-Whitney检验和配对Wilcoxon检验。为描述结果，使用了以下参数：观察次数（n）、中位数、四分位数间距和最小-最大范围。

结果

Panagen与化疗联合使用时表现出明显的白细胞刺激和白细胞保护作用。在一个辅助方案中，分析了片剂形式的Panagen的抗癌作用。我们发现Panagen有助于维持治疗前固有抗肿瘤免疫的活性水平，并诱导细胞毒性CD8+穿孔素+T细胞外周池的形成。我们的3年随访分析表明，接受Panagen治疗的患者中有24%在治疗后复发或死亡，而安慰剂组为45%。

结论

该试验收集的数据表明Panagen是一种多方面的“一体化”药物，能够同时维持造血功能，使固有免疫细胞免受连续三轮化疗的不良反应影响，并增强个体适应性免疫。其独特之处在于它通过胃肠道给药，并通过肠黏膜淋巴系统发挥作用。总体而言，治疗后固有免疫初始水平的维持、适应性细胞毒性免疫反应的发展以及3年后复发率的显著降低都证明了Panagen的抗癌活性。