5-aminolevulinic-acid-hexyl-ester and Papillomavirus-Infections

Current treatments for high-grade cervical intraepithelial neoplasia (CIN2/3) are mainly excisional procedures, which are associated with significant side effects and pose risks for future pregnancies. An effective and safe therapy is needed to reduce the requirement for surgical interventions in women of reproductive age.. This review looks at the pharmacokinetic and clinical data for topical hexaminolevulinate (HAL) photodynamic therapy (PDT), which is currently entering late phase clinical trials for high-grade CIN. The authors include published studies in patients and volunteers but laboratory and animal studies have been excluded as have studies on other porphyrins such as Photofrin, 5-aminolevulinic acid, methyl aminolevulinate and studies reporting other clinical applications for HAL.. Topical HAL PDT has potential as a non-surgical tissue-preserving treatment for CIN and persistent oncogenic human papilloma virus infections. HAL PDT selectively treats the entire epithelial sheet, without the tissue destruction seen in excisional procedures. The authors believe that this treatment could replace surgery in a large proportion of patients. It would be of particular value to the high percentage of women who are interested in future child-bearing. If the treatment is approved, it is very likely that physicians will want to use this treatment, as many patients will be keen to consider a non-surgical option.

Topics: Aminolevulinic Acid; Female; Humans; Papillomavirus Infections; Photochemotherapy; Photosensitizing Agents; Uterine Cervical Dysplasia

High-risk human papilloma virus (HPV)-associated cervical cancer is the fourth most common cancer in women worldwide. Current treatments of high-grade squamous intraepithelial lesion (HSIL) of the cervix are based on invasive surgical interventions, compromising cervical competence and functionality. APRICITY is a multicentre, prospective, double-blind, randomised controlled phase 3 study further evaluating the efficacy and safety of Cevira, an integrated drug-delivery and light-delivery device for hexaminolevulinate photodynamic therapy, which shows promise as a novel, non-invasive outpatient therapy for women with HSIL.. Patients with biopsy-confirmed HSIL histology are invited to participate in the study planned to be conducted at 47 sites in China and 25 sites in Ukraine, Russia and the European Union. The aim is to include at least 384 patients, which will be randomised to either Cevira or placebo group (2:1). All patients will be assessed 3 months after first treatment and a second treatment will be administered in patients who are HPV positive or have at least low-grade squamous intraepithelial lesion. Primary endpoint is the proportion of the responders 6 months after first treatment. Secondary efficacy and safety endpoints will be assessed at 6 months, and data for secondary performance endpoints of the Cevira device will be collected at 3 months and 6 months, in case second treatment was administered. All patients in the Cevira group will be enrolled in an open, long-term extension study for 6 months to collect additional efficacy and safety data (study extension endpoints).. The study was approved by the ethics committee of the Peking Union Medical College Hospital and Hannover Medical University, Germany. Findings will be disseminated through peer review publications and conference presentations.. NCT04484415; clinicaltrials.gov.

Topics: Aminolevulinic Acid; Carcinoma in Situ; Clinical Trials, Phase III as Topic; Female; Humans; Multicenter Studies as Topic; Papillomavirus Infections; Photochemotherapy; Prospective Studies; Randomized Controlled Trials as Topic; Squamous Intraepithelial Lesions; Uterine Cervical Neoplasms

Cervical intraepithelial neoplasia (CIN) 1-3 is the precursor of invasive cervical cancer and associated with human papillomavirus infection. Standard treatment is surgical and may be associated with subsequent pregnancy complications. Photodynamic therapy (PDT) of CIN may be an interesting alternative.. Patients were treated by PDT using hexaminolevulinate (HAL) and methylaminolevulinate in six dose and light groups and two incubation periods in a double-blind setting. Follow-up examinations were performed after 3, 6, and 12 months with histology, cytology, and HPV testing.. We included eight patients with CIN1, 23 with CIN2, and 36 with CIN3. Treatment was well tolerated. HAL 40 mM with 3-hour application turned out to be the most-effective group with 67% (10/15) complete response rate. The combined complete and partial response for patients with CIN2 was 83% (20/24).. PDT with CIN may be a safe and effective procedure for CIN treatment.

Topics: Adult; Aminolevulinic Acid; Double-Blind Method; Female; Humans; Papillomavirus Infections; Photochemotherapy; Photosensitizing Agents; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

CIN is a disease of women in their reproductive years, and treatment includes excisional techniques with increased risk of preterm deliveries. Photodynamic therapy (PDT) using topical precursor of photoactive porphyrins may be a non-invasive alternative with minimal side effects. This study assessed the feasibility and response rate of PDT with hexaminolevulinate (HAL) in cervical intraepithelial neoplasia (CIN) and human papillomavirus (HPV) infection.. Twenty four patients with a CIN 2 or 3 or a persistent CIN 1 and a positive high-risk HPV-DNA test were included. Each patient had gynaecologic examination including cervical cytology, HPV DNA testing, colposcopy and biopsy. Ten milliliters of HAL-thermogel (10 mM) were topically applied to the cervix for 3-5 hours, followed by 1,000 seconds of illumination of both ecto- and endocervical canal with red coherent light (wave length 633 nm) using a PDT laser and a special light catheter. Follow-up examinations were carried out after 3 (cytology, colposcopy, HPV DNA testing, and if needed re-PDT) and 6 months.. Seven, 10, and 7 patients had a CIN 1, 2, or 3, respectively. Treatment could be accomplished in all cases and no severe side effects were encountered. Fifteen out of the 24 patients had a complete response (15/24 = 63%) and a HPV remission 6 months after 1-3 treatments. The remission rates were 71%, 50%, and 71% for CIN 1, 2 and 3.. HAL PDT seems to be a non-invasive, repeatable procedure for CIN and cervical HPV infection with minimal side effects which can be easily performed on outpatient basis.

Topics: Adult; Aminolevulinic Acid; Feasibility Studies; Female; Humans; Papillomavirus Infections; Photochemotherapy; Photosensitizing Agents; Treatment Outcome; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms; Young Adult