Low-Dose Topical Delivery of All-Trans Retinoic Acid for Cervical Intraepithelial Neoplasia II and III

Abstract

Objective: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III. Methods: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks. Results: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities. Conclusion: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

Retinoids in cancer chemoprevention and therapy: Meta-analysis of randomized controlled trials

“…Pooled data in 13 studies ( Fenaux et al, 2000 ; Motzer et al, 2000 ; Bodsworth et al, 2001 ; Follen et al, 2001 ; Atzpodien et al, 2004 ; Fosså et al, 2004 ; Ruffin et al, 2004 ; Shen et al, 2004 ; Burnett et al, 2007 ; Arrieta et al, 2010 ; Burnett et al, 2010 ; Nazha et al, 2013 ; Sanusi, 2019 ) with 2,640 patients showed that retinoids group exhibited a better clinical response rate than control group (RR = 1.24, 95% CI = 1.03–1.49, p = 0.02) ( Figure 2B ). Heterogeneity among the above 13 studies was significant (I 2 = 63%) ( Figure 2B ).…”

“…The literature searching and screening process is presented in Figure 1 . Thirty-nine RCT studies with a total of 15,627 patients were included in this meta-analysis ( Fenaux et al, 2000 ; Kohler et al, 2000 ; Motzer et al, 2000 ; van Zandwijk et al, 2000 ; Bodsworth et al, 2001 ; Follen et al, 2001 ; Lippman et al, 2001 ; Bernstein et al, 2002 ; George et al, 2002 ; Robinson et al, 2002 ; Atzpodien et al, 2004 ; Fosså et al, 2004 ; Ruffin et al, 2004 ; Shen et al, 2004 ; Toma et al, 2004 ; Aass et al, 2005 ; Chiesa et al, 2005 ; Perry et al, 2005 ; Richtig et al, 2005 ; Takai et al, 2005 ; Khuri et al, 2006 ; Scardina et al, 2006 ; Veronesi et al, 2006 ; Burnett et al, 2007 ; Sabichi et al, 2008 ; Decensi et al, 2009 ; Weinstock et al, 2009 ; Andrijono and Muhilal, 2010 ; Arrieta et al, 2010 ; Burnett et al, 2010 ; Lee et al, 2010 ; Rao et al, 2011 ; Kadakia et al, 2012 ; Weinstock et al, 2012 ; Douer et al, 2013 ; Nazha et al, 2013 ; Shinagawa et al, 2014 ; Aviles et al, 2015 ; Okita et al, 2015b ; Bhatia et al, 2017 ; Sanusi, 2019 ). The characteristics of the included studies are shown in Table 1 .…”

“…The literature searching and screening process is presented in Figure1. Thirty-nine RCT studies with a total of 15,627 patients were included in this meta-analysis(Fenaux et al, 2000;Kohler et al, 2000;Motzer et al, 2000;van Zandwijk et al, 2000;Bodsworth et al, 2001;Follen et al, 2001;Lippman et al, 2001;Bernstein et al, 2002;George et al, 2002;Robinson et al, 2002;Atzpodien et al, 2004;Fosså et al, 2004;Ruffin et al, 2004;Shen et al, 2004;Toma et al, 2004;Aass et al, 2005;Chiesa et al, 2005; Perry et al, 2005;Richtig et al, 2005;Takai et al, 2005; Khuri et al, 2006;Scardina et al, 2006;Veronesi et al, 2006;Burnett et al, 2007;Sabichi et al, 2008;Decensi et al, 2009; Weinstock et al, 2009;Andrijono and Muhilal, …”

A Scoping Review of Complementary and Alternative Medicine for Human Papillomavirus Infections and Cervical Dysplasia

“…Topical therapies with reported adverse events were Paiteling, silicon dioxide and sodium selenite (SAM) gel, Coriolus versicolor, vitamin A, Praneem, myrtle, gongjingkang, polyphenon E, curcumin, and terameprocol. Side effects from these therapies included from vaginitis symptoms, 13 vaginal discharge, 28 erythema, 28 vaginal burning, 14,23,28,32,49 and itching. 14,23,28,32,56 No studies of topical agents used a scale to measure adverse events.…”

“…Side effects from these therapies included from vaginitis symptoms, 13 vaginal discharge, 28 erythema, 28 vaginal burning, 14,23,28,32,49 and itching. 14,23,28,32,56 No studies of topical agents used a scale to measure adverse events. Only 5 studies discussed the process used to evaluate adverse events including the following: blood samples, 15,49 questionnaires, 28,59 and clinical assessment or interview from study investigators.…”