A phase I study of an oral selective gamma secretase (GS) inhibitor RO4929097 in combination with neoadjuvant paclitaxel and carboplatin in triple negative breast cancer

We present the results of a phase I study of an oral selective gamma secretase (GS) inhibitor (critical to Notch signaling), RO4929097 in combination with neoadjuvant chemotherapy for operable triple negative breast cancer. The primary objective was to determine the maximum tolerated dose (MTD) of RO4929097. Secondary objectives were to determine real-time pharmacokinetics of RO4929097 and paclitaxel, safety and pathologic (pCR) complete response to study treatment. Eligible patients, initiated carboplatin at AUC 6 administered intravenously (IV) on day 1, weekly paclitaxel at 80  mg/m2 IV and RO4929097 10 mg daily given orally (PO) on days 1–3, 8–10 and 15–17 for six 21-day cycles. RO4929097 was escalated in 10 mg increments using the 3 + 3 dose escalation design. Two DLTs were observed in 14 patients - Grade (G) 4 thrombocytopenia in dose level 1 (10 mg) and G3 hypertension in dose level 2 (20 mg). Protocol-defined MTD was not determined due to discontinuation of RO4929097 development. However, 4 of 5 patients enrolled to 20 mg dose of RO4929097 required dose reduction to 10 mg due to toxicities (including neutropenia, thrombocytopenia and hypertens ion) occurring during and beyond the DLT observation period. Thus, 10 mg would have been the likely dose level for further development. G3 or higher hematologic toxicities included neutropenia (N = 8, 57%) and thrombocytopenia (N =&...
Source: Investigational New Drugs - Category: Drugs & Pharmacology Source Type: research

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Discussion Syphilis is caused by the spirochete Treponema pallidum. It is a very old disease that despite understanding the organism and readily available treatment, still causes disease. Syphilis is transmitted sexually. According to the Centers for Disease Control, “[i]n 2018, a total of 35,063 cases of [Primary and Secondary] syphilis were reported in the United States, yielding a rate of 10.8 cases per 100,000 population …. This rate represents a 14.9% increase compared with 2017 (9.4 cases per 100,000 population), and a 71.4% increase compared with 2014 (6.3 cases per 100,000 population).” The incre...
Source: PediatricEducation.org - Category: Pediatrics Authors: Tags: Uncategorized Source Type: news
Skeletal muscle atrophy is a major consequence of several pathophysiological conditions, including neuromuscular diseases, disuse (limb immobilization, space flight), aging (sarcopenia) and other wasting conditions (i.e. cancer cachexia). Basically, a disequilibrium between anabolic/catabolic pathways leads to progressive loss of muscle mass and functional impairment. The aim of translational research in this field is to identify anabolic compounds able to support protein synthesis and muscle mass, restoring muscle function and metabolism.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
We report our case, along with the relevant literature. The patient is a 70-year-old man. Twelve years ago, he was diagnosed with anti-acetylcholine receptor antibody (anti-Ach-R Ab)-positive systemic MG. He underwent thymectomy and was treated with oral steroids.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Dermatomyositis (DM) is a rare and systemic autoimmune disease belonging to the idiopathic inflammatory myopathies, primarily affecting skeletal muscle and skin. However, other organs might be affected, like the lung, heart or arteries, and development of cancer might also be associated with DM. For diagnostic and prognostic management, the detection of one of the associated autoantibodies (aAB, e.g. Mi-2, NXP-2, MDA5 TIF1 γ and rarely SAE) is of outmost importance, since associations between these antibodies and interstitial lung disease (ILD) or cancer (e.g.
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
Inflammatory myopathies consist of heterogenous group of immune-mediated muscle diseases including dermatomyositis, polymyositis and so on. Patients with inflammatory myopathies occasionally have malignancies such as breast, lung, colorectal cancer and nasopharyngeal carcinoma. There have been a few reports of patients with inflammatory myopathy and lymphoma. Herein, we report an unusual case of a 67-year-old male with inflammatory myopathy and diffuse large B cell lymphoma who initially presented with slowly progressive quadriparesis, axial weakness and abnormality in the electromyography and muscle magnetic resonance image (MRI).
Source: Neuromuscular Disorders - Category: Neurology Authors: Source Type: research
SUPPLEMENTS could be used to lower your risk, or even prevent some high blood pressure symptoms. This is the "most effective natural remedy" to avoid the deadly signs and symptoms of hypertension. Should you consider adding calcium supplements to your diet, to prevent deadly high blood pressure symptoms?
Source: Daily Express - Health - Category: Consumer Health News Source Type: news
The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-Poly (D, L-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity.Significance: The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug.Methods: The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition,...
Source: Drug Development and Industrial Pharmacy - Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research
PMID: 32976788 [PubMed - as supplied by publisher]
Source: Health Physics - Category: Physics Authors: Tags: Int J Radiat Oncol Biol Phys Source Type: research
Authors: Kato M, Sugimoto A, Atsumi T Abstract INTRODUCTION: Pulmonary arterial hypertension (PAH), also referred to as group 1 pulmonary hypertension, occurs either primarily or in association with other diseases such as connective tissue diseases (CTD). Of CTD, systemic sclerosis (SSc), systemic lupus erythematosus and mixed connective tissue disease are commonly accompanied with PAH. It is of note that SSc-PAH is associated with distinctive histopathology, an unfavorable outcome, and a blunted responsiveness to modern PAH therapies. AREAS COVERED: The data in articles published until May 2020 in peer-reviewe...
Source: Expert Review of Clinical Immunology - Category: Allergy & Immunology Tags: Expert Rev Clin Immunol Source Type: research
BOWEL cancer symptoms include weight loss, stomach pain, and feeling very tired for no obvious reason. But you could also be at risk of the disease if you notice a change to your toilet habit. These are the two colours of poo that could be caused by something serious. Should you check the colour of your stools?
Source: Daily Express - Health - Category: Consumer Health News Source Type: news
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