Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial.

BACKGROUND: A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL). METHODS: In this international multicenter randomized, placebo-controlled phase III trial at clinical centers in Switzerland, Germany and Austria, we plan to include 540 patients with primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low- or high-grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer. Patients are randomized in a 1:1 ratio into two groups: receiving blinded study treatment (letrozole or placebo tablets). When assuming a HR of 0.7, a median PFS of 18 months in the control arm and a median PFS of 25.7 months in the treatment arm, a two-sided alpha level of 5%, 3.5 years recruitment and 1.5 years observation time, we expect 330 events to have occurred within these 5 years in the total cohort yielding a power of 90%. Follow-up data for the whole cohort will be collected for up to 10 years and for the low-grade cancer for up to 12 years. DISCUSSION: The here proposed randomized phase III trial aims to identify patients with EOC in the maintenance setting, who benefit from the effectiveness of the letrozole, by proving its efficacy whilst maintaining a high standard of QoL due to the limited toxicity expected in comparison to the current alternative drugs on the market for this treatment phase. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov under the identifier NCT04111978 . Registered 02 October 2019.

Efficacy and safety of P11-4 for the treatment of periodontal defects in dogs.

OBJECTIVES: This study's aim was to investigate the safety and performance of a self-assembling peptide matrix (SAPM) P11-4 for the treatment of periodontal disease in a controlled pre-clinical study. MATERIALS AND METHODS: Acute buccal bony dehiscence defects (LxW: 5 × 3 mm) were surgically created on the distal root of four teeth on one mandible side of 7 beagle dogs followed by another identical surgery 8 weeks later on the contralateral side. SAPM P11-4 (with and without root conditioning with 24% EDTA (T1, T2)), Emdogain® (C) and a sham intervention (S) were randomly applied on the four defects at each time point. Four weeks after the second surgery and treatment, the animals were sacrificed, the mandibles measured by micro-computed tomography (µ-CT) and sections of the tissue were stained and evaluated histologically. RESULTS: Clinically and histologically, no safety concerns or pathological issues due to the treatments were observed in any of the study groups at any time point. All groups showed overall similar results after 4 and 12 weeks of healing regarding new cementum, functionality of newly formed periodontal ligament and recovery of height and volume of the new alveolar bone and mineral density. CONCLUSION: A controlled clinical study in humans should be performed in a next step as no adverse effects or safety issues, which might affect clinical usage of the product, were observed. CLINICAL RELEVANCE: The synthetic SAPM P11-4 may offer an alternative to the animal-derived product Emdogain® in the future.

Hydroxyapatite and Self-Assembling Peptide Matrix for Non-Oxidizing Tooth Whitening.

OBJECTIVES: The aim of this combined in vitro and in vivo study was to evaluate the efficacy of tooth whitening using a mixture of Self- Assembling Peptide Matrix (SAPM) and hydroxyapatite (HA). METHODS: The mixture was applied on stained bovine teeth, and the tooth color was measured using a spectrophotometer; mean changes in L*a*b values between measurements were expressed as DE. Additionally, the nature of the surface layer was investigated by ATRFTIR and EDX. The optical changes due to the additional surface layer were measured using a goniometer. Finally, a proof-of-concept clinical study was performed investigating the mixture of SAPM+HA. RESULTS: The results verified that the SAPM remained on the tooth surface and acted as a temporary adhesive to attach the HA particles to the tooth surface. Further, the optical changes due to the additional surface layer indicated a diffuse reflection to be the origin of the optical whitening. Lastly, the mixture of SAPM+HA showed significant and visible whitening after one application, increasing throughout the first week of home application (DE = 4.9 ± 3.3) and remaining stable for 30 days (DE = 4.8 ± 3.6). CONCLUSIONS: The combination of SAPM+HA particles caused optical whitening based on diffuse reflection by the HA particles on the tooth surface. The whitening effect and its magnitude observed in vitro were also seen in vivo.

Remineralizing potential of the biomimetic P11-4 self-assembling peptide on noncavitated caries lesions: A retrospective cohort study evaluating semistandardized before-and-after radiographs.

BACKGROUND: Self-assembling peptide (SAP) P11-4 was introduced to treat initial caries lesions by means of guiding hydroxyapatite regeneration within the lesion. The objective of this study was to assess its effectiveness in a practical clinical setting. METHODS: Caries lesions in permanent teeth treated with monomeric and polymeric SAP P11-4 from May 2015 through October 2020 were retrospectively analyzed at lesion and child levels by means of bite-wing radiography for changes in stage and cavitation and restoration. RESULTS: Two hundred and nineteen children aged 10 through 19 years with a total of 405 proximal lesions in posterior teeth were followed from 0.4 through 5.5 years (median, 7 months; interquartile range, 6-19 months). Regression occurred in 37% of stage RA1 (radiolucency in the outer one-half of enamel) (95% CI, 31% to 44%), 38% of stage RA2 (radiolucency in the inner one-half of enamel plus or minus the enamel-dentin junction) (95% CI, 30% to 45%), and 40% of stage RA3 (radiolucency limited to the outer one-third of dentin) (95% CI, 16% to 68%) lesions. The proportion of lesions with no cavitation was 0.96 (95% CI, 0.94 to 0.98) after 1 year and 0.91 (95% CI, 0.88 to 0.95) after 2 years. CONCLUSIONS: Real-world clinical data indicate that SAP P11-4 can lead to recovery and a healthier tooth stage. PRACTICAL IMPLICATIONS: SAP P11-4 is a safe treatment for initial caries lesions in permanent teeth that remineralizes in the deepest zone of the lesion and can be introduced easily into routine dental practice.

Cost-utility analysis of risk-reducing strategies to prevent breast and ovarian cancer in BRCA-mutation carriers in Switzerland.

OBJECTIVE: We aimed to identify the most cost-effective of all prophylactic measures available in Switzerland for women not yet affected by breast and ovarian cancer who tested positive for a BRCA1/2 mutation. METHODS: Prophylactic bilateral mastectomy (PBM), salpingo-oophorectomy (PBSO), combined PBM&PBSO and chemoprevention (CP) initiated at age 40 years were compared with intensified surveillance (IS). A Markov model with a life-long time horizon was developed from the perspective of the Swiss healthcare system using mainly literature-derived data to evaluate costs, quality-adjusted life years (QALYs) and survival. Costs and QALYs were discounted by 3% per year. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. RESULTS: All prophylactic measures were found to be cost-saving with an increase in QALYs and life years (LYs) compared to IS. PBM&PBSO were found to be most cost-effective and dominated all other strategies in women with a BRCA1 or BRCA2 mutation. Lifetime costs averaged to 141,293 EUR and 14.5 QALYs per woman with a BRCA1 mutation under IS, versus 76,639 EUR and 19.2 QALYs for PBM&PBSO. Corresponding results for IS per woman with a BRCA2 mutation were 102,245 EUR and 15.5 QALYs, versus 60,770 EUR and 19.9 QALYs for PBM&PBSO. The results were found to be robust in sensitivity analysis; no change in the dominant strategy for either BRCA-mutation was observed. CONCLUSION: All more invasive strategies were found to increase life expectancy and quality of life of women with a BRCA1 or BRCA2 mutation and were cost-saving for the Swiss healthcare system compared to IS.

Randomized Clinical Trial investigating Self-Assembling Peptide P11-4 for Treatment of Early Occlusal Caries.

Non-invasive caries treatment is a major focus in modern dentistry. The present study was designed to evaluate the effectiveness of monomeric self-assembling peptide P11-4 (SAP P11-4) in combination with fluoride varnish or polymeric self-assembling peptide matrix (SAPM) in treatment of non-cavitated occlusal caries. Ninety children and adolescents were included in this randomized, gold-standard-controlled clinical trial. Test Group 1 received SAP P11-4 and twice fluoride varnish at baseline and Day 180, Test Group 2 received SAP P11-4 on baseline and twice weekly SAPM (home-application), and Control Group received fluoride varnish on baseline and Day 180. Caries progression was measured by laser fluorescence, Nyvad Caries Activity, ICDAS-II-codes, and investigator assessments. Laser fluorescence changes demonstrated superior results for Test Group 1 and 2, as values decreased compared to an increase for the Control Group (p < 0.0005). ICDAS-II codes at Day 360 showed partial regression for Test Group 1 (6.7%) and Test Group 2 (20.0%) and partial progression for Control Group (23.3%) (p < 0.01). Nyvad Caries Activity yielded superior caries inactivation for Test Groups, compared to Control Group (p = 0.002). This trial showed that SAP P11-4, applied either in combination with fluoride varnish or twice weekly SAPM, was a superior treatment for early caries compared to fluoride varnish alone.

Efficacy of P11-4 for the treatment of initial buccal caries: a randomized clinical trial.

To investigate the safety and efficacy of Self-Assembling Peptide P11-4 (SAP P11-4) compared to placebo or fluoride varnish (FV), a randomized, controlled, blinded, split-mouth study with sequential design was conducted. Subjects presenting two teeth with White-Spot-Lesions (WSLs) were included and teeth were randomly assigned to test or control. Control received placebo at baseline (D0) and test SAP P11-4, all received FV at Day 90 (D90). Standardized photographs were taken at each visit, and WSL size changes were morphometrically assessed. Hierarchical Linear Modelling, considering paired and sequential design, was used to test four hypotheses. SAP P11-4 lesions (test, D90-D0) showed significant WSL size reduction compared to placebo (control, D90-D0; p = 0.008) or FV (control, D180-D90; p = 0.001). Combination of SAP P11-4 and delayed FV after 90 days (test, D180-D0), showed a significant difference compared to FV alone (control D270-D90; p = 0.003). No significant difference on FV efficacy was found when SAP P11-4 was applied 3 months before FV (test D270-D90; control D270-D90, p = 0.70). SAP P11-4 treatment resulted in superior caries regression compared to either placebo or FV, and FV efficacy seems not to be affected by SAP P11-4. SAP P11-4 was found to be a safe and effective WSL treatment.

Self-assembling peptide matrix for treatment of dentin hypersensitivity: A randomized controlled clinical trial.

BACKGROUND: Patient-reported dentin hypersensitivity [DHS] pain is a common finding linked with periodontal disease. This pilot clinical study investigates a novel therapeutic regimen using self-assembling peptide matrix [SAPM] gel (test) compared with use of an 8% arginine and calcium carbonate [ACC] toothpaste (control) for treatment of DHS. METHODS: A total of 50 patients with history of supportive periodontal therapy were enrolled in this prospective, randomized monocentric clinical study, of which 45 (test: n = 22; control: n = 23) fulfilled all the study visits. Test group patients performed ex-office application of SAPM gel over 1 week, while control group patients performed ex-office application of ACC toothpaste over 90 days. DHS was assessed in office by Visual Analog Scale [VAS], and patient's perception of pain relief was evaluated by questionnaire. In support of the clinical data, scanning electron microscopy images were recorded to investigate tubule occlusion of both control and test product. RESULTS: Both SAPM and ACC significantly reduced DHS in patients throughout the study, with the patient questionnaire indicating higher patient satisfaction at the earlier time points for the test group. CONCLUSIONS: Both SAPM gel and ACC toothpaste were successful in providing relief from DHS and showed similar outcomes on VAS and verbal response scale (VRS) throughout the study period of 90 days. The new therapeutic regimen using SAPM resulted in higher patient satisfaction at day 7, as indicated by the patient questionnaire and the higher number of pain-free patients at day 7 and day 90. This is a pilot study describing a novel therapy for DHS.