Clinical and Molecular Responses in High-Grade Intraepithelial Neoplasia Treated with Topical Imiquimod 5

• Published in: Clinical cancer research Vol. 7; no. 10; pp. 3031 - 3033
• Main Authors: DIAZ-ARRASTIA, Concepcion, ARANY, Istvan, ROBAZETTI, Sonia C, DINH, Tung V, GATALICA, Zoran, TYRING, Stephen K, HANNIGAN, Edward
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.10.2001
• Subjects: 2',5'-Oligoadenylate Synthetase - genetics; Administration, Topical; Adult; Aminoquinolines - therapeutic use; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Cervical Intraepithelial Neoplasia - drug therapy; Cervical Intraepithelial Neoplasia - genetics; Chemotherapy; Female; Follow-Up Studies; Gene Expression Regulation, Enzymologic - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Genital Neoplasms, Female - drug therapy; Humans; Medical sciences; Middle Aged; Ointments; Pharmacology. Drug treatments; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Time Factors; Treatment Outcome; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - genetics; Vaginal Neoplasms - drug therapy; Vaginal Neoplasms - genetics; Vulvar Neoplasms - drug therapy; Vulvar Neoplasms - genetics; Antineoplastic agent; Histological grading; Human; Recurrence; Immunostimulation; Immune response; Imiquimod; Toxicity; Treatment efficiency; Biological marker; Vagina; Vulva; Uterine cervix; Malignant tumor; Epithelium; Female genital diseases; Percutaneous route; Chemotherapy; Treatment; Uterine cervix diseases; Topical administration
• ISSN: 1078-0432; 1557-3265

Objective: To assess the clinical and molecular response of patients with recurrent high-grade vulvar, vaginal, or cervical intraepithelial neoplasia treated with topical 1–2(2-methylpropyl)-1 H -imidazo [4,5- c ] quinolin-4-amine (imiquimod) cream 5%, an immune response modifier with known efficacy in the treatment of external genital warts. Methods: This is the first case series in the peer-reviewed literature reporting the use of imiquimod in high-grade intraepithelial neoplasia of the lower genital tract. Eight patients with high-grade intraepithelial neoplasia were treated with imiquimod in the gynecological oncology clinic and the HIV gynecology clinic at The University of Texas Medical Branch at Galveston. Frozen biopsies were available for RNA extraction on four patients before and after therapy. Using semiquantitative reverse transcription-PCR, we measured RNA levels of IFNs α and γ, 2′,5′-oligoadenylate synthetase, as well as CD4 and CD8 lymphocyte markers. Results: Of the patients treated, four had complete responses, two had partial responses, one progressed, and one did not tolerate the therapy. Of the four complete responders, two remained disease-free (mean follow-up, 33 months). 2′,5′-Oligoadenylate synthetase RNA expression showed an increased trend after therapy. Conclusions: These results obtained in this small and heterogeneous group merit further study in the use of topical 5% imiquimod use in the treatment of intraepithelial neoplasia. An important mechanism of action of imiquimod may involve 2′,5′-oligoadenylate synthetase antiviral activity.