Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial

Koeneman, Margot M.; Kruse, Arnold‐Jan; Kooreman, Loes; Hausen, Axel zur; Hopman, Anton H. N.; Sep, Simone J. S.; Gorp, Toon Van; Slangen, Brigitte; Beekhuizen, Heleen J. van; Sande, A. J. M. van de; Gerestein, C.G.; Nijman, Hans W.; Kruitwagen, Roy F.P.M.

doi:10.1186/s12885-017-3108-9

Cited by 18 publications

(28 citation statements)

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“…Because of local and systemic side effects Imiquimod is inappropriate for the treatment of CIN1 [35]. A new trial with Imiquimod for CIN2 + had to be stopped due to the lack of appropriate patients to be included in the study, because many preferred either the Large Loop Excision of the Transformation Zone (LLETZ) procedure or the Imiquimod treatment [36].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

Major

Dvořák²,

Schwarzová³

et al. 2020

Arch Gynecol Obstet

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Purpose The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. Methods 216 women aged 25–60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. Results Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. Conclusion SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. Trial registration number ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040; retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

Major

Dvořák²,

Schwarzová³

et al. 2020

Arch Gynecol Obstet

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“…Imiquimod is a TLR7 agonist with proven antitumor activity as a topical treatment for skin cancer. At the moment, it is approved by US FDA and many phase 2 clinical trials show its safety and efficacy in other types of cancer, such as carcinoma in situ bladder cancer [112], cervical intraepithelial neoplasia [113], or breast cancer cutaneous metastases [114].…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-Like Receptors in Actuating Stem/Progenitor Cell Repair Mechanisms: Different Functions in Different Cells

Sallustio

Curci

Stasi

et al. 2019

Stem Cells International

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Toll-like receptors (TLRs) represent one of the bridges that regulate the cross-talk between the innate and adaptive immune systems. TLRs interact with molecules shared and preserved by the pathogens of origin but also with endogenous molecules (damage/danger-associated molecular patterns (DAMPs)) that derive from injured tissues. This is probably why TLRs have been found to be expressed on several kinds of stem/progenitor cells (SCs). In these cells, the role of TLRs in the regulation of the basal motility, proliferation, differentiation processes, self-renewal, and immunomodulation has been demonstrated. In this review, we analyze the many different functions that the TLRs assume in SCs, pointing out that they can have different effects, depending on the background and on the kind of ligands that they recognize. Moreover, we discuss the TLR involvement in the response of SC to specific tissue damage and in the reparative processes, as well as how the identification of molecules mediating the differential function of TLR signaling could be decisive for the development of new therapeutic strategies. Considering the available studies on TLRs in SCs, here we address the importance of TLRs in sensing an injury by stem/progenitor cells and in determining their behavior and reparative activity, which is dependent on the conditions. Therefore, it could be conceivable that SCs employed in therapy could be potentially exposed to TLR ligands, which might modulate their therapeutic potential in vivo. In this context, to modulate SC proliferation, survival, migration, and differentiation in the pathological environment, we need to better understand the mechanisms of action of TLRs on SCs and learn how to control these receptors and their downstream pathways in a precise way. In this manner, in the future, cell therapy could be improved and made safer.

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“…Previous studies have investigated the effect of imiquimod in CIN and showed the adverse effects to be well-tolerated [ 4 , 5 ]. Currently, a non-randomised study comparing the effectiveness of imiquimod treatment with large loop excision of the transformation zone (LLETZ) is being performed in the Netherlands (TOPIC-3) [ 6 ]. The patients were instructed to administer one sachet containing 12,5 mg of 5% imiquimod with a vaginal applicator three times weekly intravaginally.…”

Section: Introductionmentioning

confidence: 99%

Systemic adverse events in imiquimod use for cervical intraepithelial neoplasia – A case series

Wouters

Hendriks

Koeneman

et al. 2019

Case Reports in Women's Health

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Treatment for cervical intraepithelial neoplasia (CIN) often consists of an excisional procedure. However, less invasive treatment methods have been explored, such as topical treatment with imiquimod cream. Imiquimod has been proven to be effective in the regression of vulvar intraepithelial neoplasia (VIN) and vaginal intraepithelial neoplasia (VAIN). Previous studies have investigated the effect of imiquimod in CIN and showed well tolerated adverse effects. During a current study in the Netherlands, a number of adverse events have occurred. This case series presents a selection of these. Gynaecologists should be aware of the possible adverse effects of topical treatment with imiquimod cream.

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Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial

Cited by 18 publications

References 1 publication

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial

Role of Toll-Like Receptors in Actuating Stem/Progenitor Cell Repair Mechanisms: Different Functions in Different Cells

Systemic adverse events in imiquimod use for cervical intraepithelial neoplasia – A case series

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