A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3) Journal Article
| Authors: | Trimble, C. L.; Levinson, K.; Maldonado, L.; Donovan, M. J.; Clark, K. T.; Fu, J.; Shay, M. E.; Sauter, M. E.; Sanders, S. A.; Frantz, P. S.; Plesa, M. |
| Article Title: | A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3) |
| Abstract: | Objective: Most treatment options for cervical intraepithelial neoplasia 2/3 (CIN2/3) are either excisional or ablative, and require sequential visits to health care providers. Artesunate, a compound that is WHO-approved for treatment of acute malaria, also has cytotoxic effect on squamous cells transformed by HPV. We conducted a first-in-human Phase I dose-escalation study to assess the safety and efficacy of self-administered artesunate vaginal inserts in biopsy-confirmed CIN2/3. Methods: Safety analyses were based on patients who received at least one dose, and were assessed by the severity, frequency, and duration of reported adverse events. Tolerability was assessed as the percentage of subjects able to complete their designated dosing regimen. Modified intention-to-treat analyses for efficacy and viral clearance were based on patients who received at least one dose for whom endpoint data were available. Efficacy was defined as histologic regression to CIN1 or less. Viral clearance was defined as absence of HPV genotoype (s) detected at baseline. Results: A total of 28 patients received 1, 2, or 3 five-day treatment cycles at study weeks 0, 2, and 4, respectively, prior to a planned, standard-of-care resection at study week 15. Reported adverse events were mild, and self-limited. In the modified intention-to-treat analysis, histologic regression was observed in 19/28 (67.9%) subjects. Clearance of HPV genotypes detected at baseline occurred in 9 of the 19 (47.4%) subjects whose lesions underwent histologic regression. Conclusions: Self-administered vaginal artesunate inserts were safe and well-tolerated, at clinically effective doses to treat CIN2/3. These findings support proceeding with Phase II clinical studies. © 2020 Elsevier Inc. |
| Keywords: | adult; cancer chemotherapy; clinical article; middle aged; cancer surgery; young adult; drug tolerability; drug efficacy; drug safety; drug withdrawal; multiple cycle treatment; gastrointestinal symptom; tinnitus; dyspareunia; vagina disease; vagina pain; vaginal dryness; chill; drug dose escalation; fever; pruritus; insomnia; urinary tract infection; anxiety disorder; flu like syndrome; headache; phase 1 clinical trial; cystitis; bacterial infection; uterine cervix carcinoma in situ; suicidal ideation; alphapapillomavirus; uterus surgery; clinical outcome; systemic disease; uterus disease; human papillomavirus type 16; human papillomavirus type 18; proof of concept; viral clearance; vaginitis; drug self administration; eczema; intention to treat analysis; human; female; priority journal; article; pelvic pain; perineal pain; artesunate; human papillomavirus type 33; human papillomavirus type 31; human papillomavirus type 35; human papillomavirus type 51; human papillomavirus type 52; human papillomavirus type 58; human papillomavirus type 59; human papillomavirus type 66; human papillomavirus type 68; cancer interception; histologic regression; hpv high grade squamous intraepithelial lesion (hsil/cin2/3); selfadministered; cervical intraepithelial neoplasia 2 3; common cold symptom; human papillomavirus type 42; human papillomavirus type 54; human papillomavirus type 62; human papillomavirus type 67; human papillomavirus type 73; human papillomavirus type 82; human papillomavirus type 83; noninfective cystitis; uterine cramping; vagina discharge (disease); vagina mycosis; vaginal pruritus; vaginal spotting; vaginal twitching |
| Journal Title: | Gynecologic Oncology |
| Volume: | 157 |
| Issue: | 1 |
| ISSN: | 0090-8258 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2020-04-01 |
| Start Page: | 188 |
| End Page: | 194 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2019.12.035 |
| PUBMED: | 32005582 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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