Effectively prevent side effects of chemotherapy, the new phase 2 clinical results are positive December 15, 2017 Source: WuXi PharmaTech BeyondSpring recently announced the results of Phase 2 of its global Phase 2/3 clinical trial (Study 105), announcing that it has achieved its primary goal and will begin Phase 3 trials soon. This study compared the efficacy of the new drug Plinabulin and long-acting colony cell stimulating factor (G-CSF) pegfilgrastim (Neulasta) in preventing neutropenia (CIN) caused by docetaxel chemotherapy. Phase 2 preliminary data for Study 105 will be presented at the 2018 ASCO-SITC Clinical Immuno Oncology Symposium in San Francisco, January 25-27, 2018. In addition, the company announced that ongoing phase 3 non-small cell lung cancer (NSCLC) clinical trials (Study 103, 138 patients enrolled in the study) showed that Plinabulin significantly reduced docetaxel CIN (p value <0.0001). Neutrophils are white blood cells and are the main means of fighting infection. Many types of cytotoxic chemotherapy kill all rapidly dividing cells, including tumor cells, as well as healthy white blood cells. The incidence of neutropenia depends to a large extent on the type of chemotherapy, the disease, and the patient's background, affecting 7% to 65% of patients receiving chemotherapy. Most chemotherapy-induced neutropenia cases occur during the first cycle of drug treatment, resulting in delayed further dosing, reduced chemotherapy dose, or early termination of chemotherapy in 10% to 20% of patients. People with neutropenia are more susceptible to bacterial infections, and if they are not treated in time, they may pose a threat to life. Approximately 20% of patients with severe neutropenia develop severe bacterial infections. Unfortunately, the initial signs of these infections can be difficult to detect because patients with a lack of immune response do not show common signs of infection, such as inflammation or fever. More than 60,000 patients are hospitalized each year for neutropenic fever, which often leads to serious infections in patients with neutropenia. The mortality rate of these patients is between 9% and 18%. Since 1988, only G-CSF has been approved for the prevention of neutropenia. Due to its side effects (such as bone pain) and its high cost as a biopharmaceutical, its use is limited and is generally used after 24 hours of chemotherapy, which is only used in about 20% of patients. ▲Plinabulin molecular structure (Source: Wikipedia) Plinabulin is a guanine nucleotide exchange factor (GEF-H1) activator that disrupts the microtubule network in the cytoskeleton and releases GEF-H1. This process activates the downstream signal transduction pathway leading to activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells, upregulates immune-related genes, and activates a series of related genes that promote dendritic cell (DC) maturation, T cell activation, and prevention of neutropenia. In each cycle, Plinabulin was administered as a single IV infusion, 30 minutes to 1 hour after completion of chemotherapy, on the day of administration, and G-CSF was administered 24 hours after chemotherapy. In addition, the use of Plinabulin has nothing to do with bone pain, which is a common side effect of G-CSF. In Study 105, Plinabulin reached the primary goal of a 3-stage dose selection. NSCLC patients were randomized to group 1 (docetaxel + pegfilgrastim (G-CSF)), group 2 (docetaxel + Plinabulin 5 mg / m 2 body surface area), group 3 (docetaxel + Plinabulin 10 mg / sf M), or group 4 (Docetaxel + Plinabulin 20 mg / m 2 ). A single dose of pegfilgrastim was administered 24 hours after docetaxel administration and Plinabulin was administered 0.5-1 hour after docetaxel administration. All patients had a docetaxel dose of 75 mg/m2. The primary end point of the study was the number of days (DSN) in which the patient experienced grade 4 neutropenia during the first treatment cycle. In Study 103, data from 138 patients showed that Plinabulin reduced the percentage of patients with grade 4 neutropenia caused by docetaxel treatment from 27.4% to 3.1% (p < 0.0001). Study 103 included NSCLC patients randomized to Plinabulin + docetaxel (n = 277) or docetaxel (n = 277). The primary endpoint was overall survival (OS) and the secondary endpoint included grade 4 neutropenia on day 8 of cycle 1 (C1D8). Plinabulin (30 mg / m 2 ) was administered on days 1 and 8 of each cycle. Before administration of Plinabulin on the 8th day, blood was drawn for neutrophil count, and thus the effect after one dose of Plinabulin was evaluated. Grade 4 neutropenia in C1D8 was defined as a neutrophil count <0.5 x 10^9 cells/liter of blood. Grade 4 neutropenia was defined as the percentage of patients who experienced a neutrophil count of less than 0.5 x 10^9 cells/liter on C1D8. To date, Plinabulin has been used in more than 270 patients worldwide and is generally well tolerated. The most common side effects of these patients are nausea, vomiting, and transient hypertension. Dr. Douglas Blayney, co-founder and board member of the National Comprehensive Cancer Network (NCCN), a leading global researcher in Research 105 and developing guidelines for the treatment of neutropenia, said. “CIN is a clinical need, and G-CSF does not adequately address this issue. There has been little innovation in G-CSF over the past three decades. Plinabulin represents a new alternative to G-CSF in the current G-CSF Market leader Neulasta has excellent target product characteristics. Study 103 measures the number of neutrophils in C1D8 on the lowest day of neutrophil count in docetaxel treatment cycle. Day 8 neutrophil count predicts patients Has a duration of grade 4 (severe) neutropenia (DSN). Therefore, the lower the neutrophil count on day 8 or the higher the level 4 neutropenia, the longer the DSN. Therefore, The collective data generated by Studies 103 and 105 proactively confirmed that Plinabulin is highly effective in preventing docetaxel CIN. Fortunately, this positive clinical data is supported by strong Plinabulin mechanism data. †▲ Dr. Huang Wei, co-founder and CEO of Wanchun Pharmaceutical Co., Ltd. (Source: Wanchun Pharmaceutical Industry Website) Dr. Huang Wei, co-founder and CEO of Wanchun Pharmaceuticals added: “Plinabulin's highly differentiated target product characteristics compared with Neulasta have attracted the attention of national health authorities such as the FDA and CFDA and renowned researchers. As a result, Wanchun Pharmaceutical is able to rapidly advance its global neutropenia project. In less than two months, we completed the registration of the last 50 patients in Study 105." Dr. Ramon Mohanlal, Chief Medical Officer of Wanchun Pharmaceuticals, concluded: “The primary primary objective of Study Phase 2 clinical data is to determine the recommended dose for the third phase of the trial. “This is also the first time that Plinabulin and Neulasta are allowed to be head-to-head. , although the sample size is relatively small. Analysis of Phase 2 clinical data supports the entry into Phase 3 studies. We believe that Plinabulin represents a breakthrough in the development of CIN indications. †We are happy to see breakthroughs in preventing CIN and expect more cancer patients to benefit from it. Reference materials: [1] BeyondSpring Meets Primary Objective in Phase II Portion of Phase II/III Trial (Study 105) with Plinabulin for the Prevention of Docetaxel Chemotherapy-Induced Neutropenia (CIN) [2] BeyondSpring's official website
Anthocyanins widely exist in flowering plants (angiosperms), and their content in plants varies greatly with varieties, seasons, climate and maturity[ 5] According to preliminary statistics, anthocyanins are contained in 27 families and 73 genera, such as purple sweet potato, grape, blood orange, red ball cabbage, blueberry, eggplant, cherry, red berry, strawberry, mulberry, hawthorn, morning glory and other plant tissues. Anthocyanins are mainly used in food coloring, dyes, medicine, cosmetics and so on.
Application
Antioxidant and free radical scavenging function Blueberry JuicePowder, Elderberry Fruit Powder, Blackcurrant Extract Powder, Black Wolfberry Extract Xi'an Tian Guangyuan Biotech Co., Ltd. , https://www.tgybiotech.com
Anthocyanins belong to bioflavonoids, and the main physiological functions of flavonoids are free radical scavenging ability and antioxidant ability. Studies have proved that anthocyanins are the most effective antioxidants and the most powerful free radical scavengers found by human beings. The antioxidant performance of anthocyanins is 50 times higher than that of VE and 20 times higher than that of VC. Purple Sweet Potato Anthocyanin products can scavenge and inhibit - Oh, H2O2 and other reactive oxygen species, especially - Oh is stronger than ascorbic acid, and the scavenging effect is dose-dependent with concentration.
Anti mutation function
The function of anthocyanins not only makes plants present colorful colors, but also active molecules with health functions such as reducing enzyme activity and anti mutation. Studies have shown that the extract with a certain concentration of anthocyanin can effectively prevent carcinogenesis at different stages, but the individual role of anthocyanin is uncertain, partly because anthocyanin is easy to degrade after bioassay after separation from other stable components such as phenols.
Application in food
With the development of science and technology, people pay more and more attention to the safety of Food Additives. The development and utilization of natural additives has become the general trend of the development and use of additives. Anthocyanins can not only be used as nutritional enhancers in food, but also as food preservatives instead of synthetic preservatives such as benzoic acid, and can be used as food colorants in ordinary drinks and food, which meets people's general requirements for natural, safe and healthy food additives.