A Multicenter, Randomized, Cross-over Phase 3 Comparing Preventive Pegylated Filgrastim and Filgrastim in Cancer Patients Receiving Myelosuppressive Chemotherapy
Neutropenia is one of the most frequent adverse effects of chemotherapy, and the main factor to limit the dosage and delay the schedule of chemotherapy. Preventive filgrastim administration has long been established as the standard of care. A pegylated filgrastim was independently developed by GeneLeuk Biopharmaceutical Co., Ltd, Shandong, China. It composed of filgrastim and a 20 kd polyethylene glycol molecule covalently bound at the N-terminal residue. Preclinical studies phase 1 and phase 2 trials have shown that pegylated filgrastim has decreased renal clearance, increased plasma half-life, and prolonged efficacy in compare with ﬁlgrastim. These characters were similar to those of Neulasta. The investigators designed a multicenter, randomized, cross-over phase Ⅲ trial to compare the efficacy and safety of a single injection of pegylated filgrastim and daily injections of ﬁlgrastim in chemotherapy naive patients receiving commonly used regimens. The hypothesis is that pegylated filgrastim is similarly effective and safe with regular filgrastim.
2020-12-29·Combinatorial chemistry & high throughput screening4区 · 医学
Synthesis of Novel Hydrazones of Levofloxacin related molecule and their In Vitro evaluation as antioxidant, and Molecular Docking Studies.
4区 · 医学
作者: Bharat B Kashid ; Jaydeo T Kilbile ; Kishor D Wani ; Suhas M Pawar ; Vijay M Khedkar ; Anil A Ghanwat
The research work aims synthesis of novel series of hydrazones, antioxidant screening, evaluate the binding affinities, and in silico methods for the identification of possible drug targets of synthesized compounds.
This report briefly explains the synthesis of novel series of hydrazones was synthesized via. hydrazinolysis of esters to obtain hydrazide, treated with aldehyde and acetophenone to get hydrazones. The spectral confirmed hydrazones exhibited excellent to comparable anti-oxidant as compaired to the standard drugs Butylated hydroxytoluene (BHT) and Ascorbic acid. Molecular docking on myeloperoxidase (MPO) demonstrated the ability of this scaffold to correctly recognize the target and engage in significant bonded and non-bonded interactions with key residues therein.
RESULTS AND DISCUSSION:
In this study, we report an effectively synthesized compounds BK-35, BK-41, BK-26, BK-28 and BK-39 showed the best DPPH radical scavenging activity. The docking results clearly showed the binding mode of hydrazones into the active site of Myeloperoxidase (MPO). An in-silico results, no any of the synthesized compounds BK24 to BK-41 violated Lipinski's rule of five (miLog P ≤ 5).
In vitro preliminary antioxidant screening results in support by in Silico binding affinity data of novel hydrazones of levofloxacin related molecules BK-24 to BK-41 reported here have emerged as excellent antioxidant agents. The inference derived from the in vitro antioxidant screening data and the quantitative insights derived from the per-residue interaction analysis with MPO enzyme, are now being fruitfully utilized for site specific mutation around the nucleus to identify selective and potent antioxidants.
2020-10-29·Scientific Reports3区 · 综合性期刊
The incidence and clinical features of PEGylated filgrastim-induced acute aortitis in patients with breast cancer
3区 · 综合性期刊
作者: Lee, Sang Yoon ; Kim, Eun Kyoung ; Kim, Ji-Yeon ; Park, Taek-kyu ; Choi, Seung-Hyuk ; Im, Young-Hyuck ; Kim, Min Yeong ; Park, Yeon Hee ; Kim, Duk-Kyung
Although PEGylated filgrastim-induced aortitis is very rare and unknown clinically, some cases were reported and increasing, especially in breast cancer patients. The present study investigated the prevalence, clinical features and treatment of aortitis induced by PEGylated filgrastim in patients with breast cancer. A total of 2068 consecutive patients who underwent neoadjuvant/adjuvant chemotherapy with PEGylated filgrastim for breast cancer were enrolled. From the medical record, clinical, laboratory, medication, and imaging evaluation findings were collected. PEGylated filgrastim-induced aortitis was established in 0.3% of the study population. Common clinical presentations included extremely high fever and chest/back pain with high levels of inflammatory markers without any signs of infection. Contrast-enhanced computed tomography scans revealed typical enhancing wall thickening and periaortic soft tissue infiltration at various levels of aorta. All patients improved rapidly after treatment with modest doses of prednisolone (0.5 mg/kg/day) without any complications. Clinicians should be aware of aortitis as a possible complication of granulocyte-colony stimulating factor therapy, especially PEGylated filgrastim, given the frequent misdiagnoses in neutropenic patients undergoing chemotherapy.
2020-07-01·Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners4区 · 医学
A castrate-resistant metastatic prostate cancer patient with severe pancytopenia, successfully treated with docetaxel chemotherapy.
4区 · 医学
作者: Anuradha Kunthur
Prognosis of metastatic castrate-resistant prostate cancer is poor with a median survival of 12 to 36 months. Bone metastasis is common, and bone marrow metastasis occurs later in the disease course. The median survival in these patients after bone marrow involvement is less than six months. We report a case of castrate-resistant prostate cancer patient presented with severe pancytopenia due to bone marrow involvement of prostate cancer, treated successfully with docetaxel chemotherapy. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 0.1 ng/ml from 1051 ng/ml.
A 70-year-old gentleman with a history of metastatic prostate cancer on androgen deprivation therapy and polycythemia vera presented to emergency room with dizziness and melena. Workup revealed severe pancytopenia with platelet count of 12k and hemoglobin of 4.5 gm/dl. Bone marrow biopsy confirmed diffuse involvement of bone marrow with prostate cancer. Prostate-specific antigen was 1051 gm/dl. Management and outcome: The patient received 14 units of packed red blood cell, 10 units of platelet transfusion within one week. Docetaxel chemotherapy was started along with thrombopoietin agonist romiplostim and pegylated filgrastim. He received five cycles of docetaxel treatment. Post chemotherapy, the patient became transfusion independent and prostate-specific antigen improved to 1.17 ng/ml from 1051 ng/ml. The patient is still alive one year after the presentation with good quality of life and the prostate-specific antigen further improved to 0.1 ng/dl.
This case suggests that selected patients with severe pancytopenia, due to bone marrow infiltration of prostate cancer, can be treated with docetaxel chemotherapy and romiplostim support with significant response. Docetaxel treatment may be beneficial to unpack the marrow and for quicker response in patients with good performance status.