Double-blind randomized placebo-controlled multicenter clinical trial (phase IIa) on diindolylmethane’s efficacy and safety in the treatment of CIN: implications for cervical cancer prevention

EPMA Journal

Evgeniya Andrianova²  Inna Apolikhina³  Ekaterina Muyzhnek¹  Igor Kuznetsov⁵  Vadim Drukh⁶  Mikhail Paltsev⁷  Vsevolod Kiselev⁶  Gennady Sukhikh³  Levon Ashrafian⁴ 

[1] CJSC “MiraxBioPharma”, 12, Kutuzovsky av., Build. 2, Moscow 121248, Russia;CJSC “IlmixGroup”, 12, Kutuzovsky av., Build. 2, Moscow 121248, Russia;Federal State Budget Institution “Research Center for Obstetrics, Gynecology and Perinatology” of the Ministry of Health of Russian Federation, 4, Akademika Oparina Str., Moscow 117198, Russia;Russian Scientific Center of Roentgenoradiology of the Ministry of Health of the Russian Federation, Moscow, 86, Profsouznaya Str., Moscow 117837, Russia;State Budgetary Educational Institution of Higher Professional Education “Moscow State Medical Stomatological University named after A.I. Evdokimov” (MSMSU) of the Ministry of Health of Russian Federation, 20 Delegatskaya Str., Build. 1, Moscow 127473, Russia;Federal State Autonomous Educational Institution of Higher Education “Peoples’ Friendship University of Russia” (PFUR), 6, Mikluho-Maklaya Str., Moscow 117198, Russia;Federal State Budget Institution «Russian Academy of Sciences», 14 Leninsky av., Moscow 119991, Russia

关键词: Predictive preventive personalized medicine;    Targeted prevention;    Clinical trial;    Diindolylmethane;    CIN II;    CIN I;    Cervical intraepithelial neoplasia;   

Others  :  1235266
DOI  :  10.1186/s13167-015-0048-9

 received in 2015-10-09, accepted in 2015-12-07,  发布年份 2015

【 摘 要 】

Background

The article presents the results of a clinical trial on the efficacy and safety of a novel pharmaceutical composition in the form of vaginal suppositories containing diindolylmethane in the course of cervical intraepithelial neoplasia (CIN) I–II conservative treatment. It offers an attractive drug therapy for more personalized prevention of cervical cancer.

Methods

A total of 78 women of reproductive age were included. This was a multicenter, randomized, placebo-controlled, double-blind, parallel-group trial with efficacy determined by histological evaluation of cervical biopsies. The efficacy of active drug treatment (100 and 200 mg/day) in both treatment groups was significantly higher in comparison with the placebo group, according to the primary efficacy end point (proportion of patients with complete CIN regression after 90–180 days of the study drug treatment).

Results

The efficacies were 100.0 % (confidence interval (CI) 95 %: 82.35–100.00 %), 90.5 % (CI 95 %: 69.62–98.83 %), and 61.1 % (CI 95 %: 35.75–82.70 %), for the high dose, low does, and placebo, respectively. Adverse events in the placebo group were reported in 22 % of patients (CI 95 %: 7.5–43.7 %); in the first treatment group (100 mg/day), adverse events were reported in 40.0 % of patients (CI 95 %: 21.1–61.3 %); in the second treatment group (200 mg/day), adverse events were reported in 42.0 % of patients (CI 95 %: 22.1–63.4 %). The differences in side effects between treatment groups treated with the active drug and placebo were statistically significant. No serious adverse events were reported in any of the groups.

Conclusions

Thus, the use of diindolylmethane in the form of intravaginal suppositories can be effective in patients with CIN I–II and is not accompanied by clinically significant side effects. This approach could be a better option for young women with CIN I–II as it takes in attention their reproductive plans.

Trial registration

ID: ChiCTR-INR-15007497 (2 December 2015)

【 授权许可】

   
2015 Ashrafian et al.

【 图 表 】

Fig. 1.

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