Oral vinorelbine and cisplatin as first-line therapy for advanced squamous NSCLC patients: a prospective randomized international phase II study (NAVoTrial 03).

OBJECTIVE: The study investigated the efficacy and safety of oral vinorelbine-cisplatin (OV-CDDP) and gemcitabine-cisplatin (GEM-CDDP) in patients with squamous non-small cell lung cancer (sq-NSCLC). PATIENTS AND METHODS: This was an open-label, prospective, multicenter, international phase II study that enrolled untreated patients with advanced sq-NSCLC. Patients were randomized to receive 3-week cycles of either 60-80 mg/m2 OV days 1 and 8 in combination with 80 mg/m2 CDDP day 1 (arm A) or 1250 mg/m2 GEM days 1 and 8 in combination with 75 mg/m2 CDDP day 1 (arm B). After four cycles, patients without disease progression continued maintenance dose of OV or GEM until progression or unacceptable toxicity. The primary objective was disease control rate (DCR). Secondary objectives included progression-free survival (PFS), time to treatment failure (TTF), overall survival (OS), safety, and quality of life (QoL). RESULTS: A total of 114 patients with sq-NSCLC were randomized, and 113 were treated (57 in arm A and 56 in arm B). DCR was high in both arms: 73.7% (95%CI: 62.4-100.0) in arm A and 75.0% (95%CI: 63.7-100.0) in arm B. Median PFS and TTF were similar in arm A and B 4.2 and 2.8 months, and 4.3 and 3.1 months, respectively. Even though the difference was not significant, the OS was 10.2 for arm A and 8.4 months for arm B. The safety profiles were consistent with the current knowledge of adverse events. QoL results revealed an improvement in patients under OV treatment. CONCLUSION: The OV-CDDP combination showed comparable efficacy to GEM-CDDP with acceptable safety profile and enhanced patients' QoL. TRIAL REGISTRATION: The study was registered under EudraCT number 2012-003531-40.

Efficacy and safety of a new 5% minoxidil formulation in male androgenetic alopecia: A randomized, placebo-controlled, double-blind, noninferiority study.

BACKGROUND: Androgenetic alopecia (AGA) is the most common cause of hair loss in men. Topical minoxidil solutions can help to treat AGA but have to be applied continuously to be effective. OBJECTIVES: A new minoxidil formulation with improved cosmetic characteristics (DC0120, Pierre-Fabre Dermatologie) was tested for noninferiority vs a comparator minoxidil product (ALOSTIL® , Johnson & Johnson) in stimulating hair growth in men with AGA. METHODS: Two 10 cm2 areas on the scalp of each subject were randomized to receive DC0120, the comparator, or one of their corresponding vehicles, applied twice per day for 16 weeks. Nonvellus target area hair count (TAHC) was measured within treatment areas at baseline (day 1) and after 8 and 16 weeks by digital phototrichogram. RESULTS: Two hundred and twenty subjects were included and randomized, of which 210 completed the study. The mean change in nonvellus TAHC between baseline and week 16 was +22.0 hairs/cm2 (95% CI: 18.1; 25.9) in the DC0120 group and +20.5 hairs/cm2 (95% CI: 16.6; 24.4) in the comparator group. The adjusted mean difference in TAHC changes between the two treatments was +1.5 hairs/cm2 (95% CI -2.3; 5.2), with the lower 95% confidence interval above the noninferiority threshold of -7 hairs/cm2 . This indicated that DC0120 was noninferior to the comparator. Both minoxidil treatments also increased nonvellus TAHC compared to vehicle groups at 8 and 16 weeks. No new safety signals were observed. CONCLUSIONS: DC0120 was as safe and effective as a similar marketed minoxidil product for stimulating hair growth in men with AGA.

Efficacy of Propranolol Between 6 and 12 Months of Age in High-Risk Infantile Hemangioma.

BACKGROUND AND OBJECTIVES: There is no consensus on optimal treatment duration for propranolol in infantile hemangioma (IH). We evaluated the efficacy and safety of oral propranolol solution administered for a minimum of 6 months up to a maximum of 12 months of age in high-risk IH. METHODS: This single-arm, open-label, phase 3 study was conducted in patients aged 35 to 150 days with high-risk IH in 10 hospitals between 2015 and 2017. The study comprised a 6-month initial treatment period (ITP) plus continuation up to 12 months of age if complete success was not achieved, a follow-up, and a retreatment period. Patients received oral propranolol twice daily (3 mg/kg per day). The primary end point was the success rate at the end of the ITP. Furthermore, the persistence of IH response and efficacy of retreatment was evaluated. RESULTS: The success rate after 6 months of treatment was 47%, increasing to 76% at the end of the ITP. Of the patients who achieved success, 68% sustained success for 3 months without treatment, and 24% required retreatment. Of the 8 patients who were retreated, 7 achieved success. Adverse events, reported by 80% of patients, were mild, which were expected in this population or known propranolol side effects. CONCLUSIONS: Oral propranolol administered beyond 6 months and up to 12 months of age meaningfully increases the success rate in high-risk IH. Success was sustained in most patients up to 3 months after stopping treatment. Retreatment was efficacious, and the safety profile satisfactory.

Pain relief of sore throat with a new anti-inflammatory throat lozenge, ibuprofen 25 mg: A randomised, double-blind, placebo-controlled, international phase III study.

OBJECTIVE: The aim of this study was to compare the efficacy and safety of a new oromucosal ibuprofen form, ibuprofen 25 mg lozenge, in single and repeat dosing for up to 4 days, to the matched placebo, in the treatment of acute sore throat pain in adults. METHODS: In this randomised, double-blind, placebo-controlled trial, adult patients with non-streptococcal sore throat and signs of moderate-to-severe associated pain (≥5 on the objective Tonsillo-Pharyngitis Assessment 21-point scale and ≥60 mm on the subjective 0-100 mm visual analogue Sore Throat Pain Intensity Scale [STPIS]) were assigned ibuprofen 25 mg (n=194) or matching placebo (n=191) lozenge treatment. Efficacy was assessed (at the investigating centre up to 2 hours after first dosing, then on an ambulatory basis) by parameters derived from patient's scores on scales of pain relief, pain intensity, and global efficacy assessment. The primary efficacy end-point was the time-weighted TOTal PAin Relief (TOTPAR) over 2 hours after first dosing using the Sore Throat Relief Scale (STRS). Safety and local tolerability were assessed. RESULTS: Ibuprofen 25 mg was superior to placebo on numerous pain relief parameters; TOTPAR was significantly higher with ibuprofen 25 mg over 2 hours after first dosing (P<.05), the effect being apparent from the first evaluation at 15 minutes (P<.05). The STPIS reduction in favour of ibuprofen 25 mg was not significant vs placebo. Mean STRS scores and patient's global efficacy assessment both reflected a higher efficacy of ibuprofen 25 mg over the 4-day treatment period with tests of statistical significance up to day 1 evening (P<.05), and, in patients with still clinically significant pain (n=128), after an average 4 days (P<.01). Ibuprofen 25 mg lozenge was well tolerated with a safety profile similar to placebo. CONCLUSION: Low-dose ibuprofen 25 mg lozenge in repeat dosing provides in adults more efficacious and rapid relief of sore throat pain and is as well tolerated as placebo. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01785862.

Safety of Oral Propranolol for the Treatment of Infantile Hemangioma: A Systematic Review.

BACKGROUND AND OBJECTIVES: Given the widespread use of propranolol in infantile hemangioma (IH) it was considered essential to perform a systematic review of its safety. The objectives of this review were to evaluate the safety profile of oral propranolol in the treatment of IH. METHODS: We searched Embase and Medline databases (2007-July 2014) and unpublished data from the manufacturer of Hemangiol/Hemangeol (marketed pediatric formulation of oral propranolol; Pierre Fabre Dermatologie, Lavaur, France). Selected studies included ≥10 patients treated with oral propranolol for IH and that either reported ≥1 adverse event or effect (AE) or planned to capture AEs. Data capture was standardized and extracted study design, demographic characteristics, IH characteristics, intervention, and safety outcomes. AEs were assigned a system organ class and preferred term. RESULTS: A total of 83 of 398 identified literature records met the inclusion criteria, covering 3766 propranolol-treated patients. The manufacturer's data for 3 pooled clinical trials (435 propranolol-treated patients) and 1 Compassionate Use Program (1661 patients) were included. AE data were reported for 1945 of 5862 propranolol-treated patients. The most frequently reported AEs included a range of sleep disturbances, peripheral coldness, and agitation. The most serious AEs (atrioventricular block, bradycardia, hypotension, bronchospasm/bronchial hyperreactivity, and hypoglycemia-related seizures) were managed by decreasing doses or temporary/permanent discontinuation of propranolol. Limitations included the variety of included study designs; monitoring, collection, and reporting of AE data; small sample sizes for some articles; and the wide scope of review. CONCLUSIONS: Oral propranolol is well tolerated if appropriate pretreatment assessments and within-treatment monitoring are performed to exclude patients with contraindications and to minimize serious side effects during treatment.

Segmentation of the Himalayas as revealed by arc-parallel gravity anomalies.

Lateral variations along the Himalayan arc are suggested by an increasing number of studies and carry important information about the orogen's segmentation. Here we compile the hitherto most complete land gravity dataset in the region which enables the currently highest resolution plausible analysis. To study lateral variations in collisional structure we compute arc-parallel gravity anomalies (APaGA) by subtracting the average arc-perpendicular profile from our dataset; we compute likewise for topography (APaTA). We find no direct correlation between APaGA, APaTA and background seismicity, as suggested in oceanic subduction context. In the Himalayas APaTA mainly reflect relief and erosional effects, whereas APaGA reflect the deep structure of the orogen with clear lateral boundaries. Four segments are outlined and have disparate flexural geometry: NE India, Bhutan, Nepal &India until Dehradun, and NW India. The segment boundaries in the India plate are related to inherited structures, and the boundaries of the Shillong block are highlighted by seismic activity. We find that large earthquakes of the past millennium do not propagate across the segment boundaries defined by APaGA, therefore these seem to set limits for potential rupture of megathrust earthquakes.