Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III.
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.


CONCLUSIONS
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.
Ruffin
Mack T
MT
Department of Family Medicine, University of Michigan, 1018 Fuller Street, Ann Arbor, MI 48109-0708, USA. mruffin@umich.edu
Bailey
Joanne M
JM
Normolle
Daniel P
DP
Michael
Claire W
CW
Bieniasz
Mary E
ME
Kmak
David C
DC
Unger
Elizabeth R
ER
Brenner
Dean E
DE
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D018890:Chemoprevention; D003127:Colposcopy; D003274:Contraceptive Devices, Female; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008875:Middle Aged; D010919:Placebos; D012307:Risk Factors; D018401:Sample Size; D014212:Tretinoin / Q000008:administration & dosage* / Q000627:therapeutic use*; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control*; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy*
D000970:Antineoplastic Agents; D010919:Placebos; D014212:Tretinoin