Ixazomib
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Ixazomib
Ixazomib (trade name Ninlaro) is a drug for the treatment of multiple myeloma, a type of white blood cell cancer, in combination with other drugs. It is taken by mouth in the form of capsules. Common side effects include diarrhea, constipation and low platelet count. Like the older bortezomib (which can only be given by injection), it acts as a proteasome inhibitor, has orphan drug status in the US and Europe, and is a boronic acid derivative. The drug was developed by Takeda. In the US, it is approved since November 2015, and in the EU since November 2016. Medical uses Ixazomib is used in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma in adults after at least one prior therapy. There are no experiences with children and youths under 18 years of age. The study relevant for approval included 722 people. In this study, ixazomib increased the median time of progression-free survival from 14.7 months (in the placebo+lenalidomide+dexamethasone ...
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Bortezomib
Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is generally used together with other medications. It is given by injection. Common side effects include nausea, diarrhea, tiredness, low platelets, fever, numbness, low white blood cells, shortness of breath, rash and abdominal pain. Other severe side effects include low blood pressure, tumour lysis syndrome, heart failure, and reversible posterior leukoencephalopathy syndrome. It is in the class of medications known as proteasome inhibitor. It works by inhibiting proteasomes, cellular complexes that break down proteins. Bortezomib was approved for medical use in the United States in 2003 and in the European Union in 2004. It is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. Medic ...
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Takeda Pharmaceutical Company
The is a Japanese multinational pharmaceutical company, with partial American and British roots. It is the largest pharmaceutical company in Asia and one of the top 20 largest pharmaceutical companies in the world by revenue (top 10 following its merger with Shire). The company has over 49,578 employees worldwide and achieved US$19.299 billion in revenue during the 2018 fiscal year. The company is focused on oncology, rare diseases, neuroscience, gastroenterology, plasma-derived therapies and vaccines. Its headquarters is located in Chuo-ku, Osaka, and it has an office in Nihonbashi, Chuo, Tokyo. In January 2012, Fortune Magazine ranked the Takeda Oncology Company as one of the 100 best companies to work for in the United States. As of 2015, Christophe Weber was appointed as the CEO and president of Takeda. History Founding and initial acquisitions (1781-2010) Takeda Pharmaceuticals was founded in 1781, and was incorporated on January 29, 1925. One of the firm's ...
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Proteasome Inhibitor
Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma. Mechanism Multiple mechanisms are likely to be involved, but proteasome inhibition may prevent degradation of pro-apoptotic factors such as the p53 protein, permitting activation of programmed cell death in neoplastic cells dependent upon suppression of pro-apoptotic pathways. For example, bortezomib causes a rapid and dramatic change in the levels of intracellular peptides. Examples * The first non-peptidic proteasome inhibitor discovered was the natural product lactacystin. * Disulfiram has been proposed as another proteasome inhibitor. * Epigallocatechin-3-gallate has also been proposed. * Marizomib (salinosporamide A) has started clinical trials for multiple myeloma. * Oprozomib (ONX-0912), delanzomib (CEP-18770) have also started clinical trials. ...
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Oral Administration
Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are intended to have a systemic effect, reaching different parts of the body via the bloodstream, for example. Oral administration can be easier and less painful than other routes, such as injection. However, the onset of action is relatively low, and the effectiveness is reduced if it is not absorbed properly in the digestive system, or if it is broken down by digestive enzymes before it can reach the bloodstream. Some medications may cause gastrointestinal side effects, such as nausea or vomiting, when taken orally. Oral administration can also only be applied to conscious patients, and patients willing and able to swallow. Terminology ''Per os'' (; ''P.O.'') is an adverbial phrase meaning literally from Latin "through the mouth" or "by mouth ...
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P-value
In null-hypothesis significance testing, the ''p''-value is the probability of obtaining test results at least as extreme as the result actually observed, under the assumption that the null hypothesis is correct. A very small ''p''-value means that such an extreme observed outcome would be very unlikely under the null hypothesis. Reporting ''p''-values of statistical tests is common practice in academic publications of many quantitative fields. Since the precise meaning of ''p''-value is hard to grasp, misuse is widespread and has been a major topic in metascience. Basic concepts In statistics, every conjecture concerning the unknown probability distribution of a collection of random variables representing the observed data X in some study is called a ''statistical hypothesis''. If we state one hypothesis only and the aim of the statistical test is to see whether this hypothesis is tenable, but not to investigate other specific hypotheses, then such a test is called a null ...
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Teratogenic
Teratology is the study of abnormalities of physiological development in organisms during their life span. It is a sub-discipline in medical genetics which focuses on the classification of congenital abnormalities in dysmorphology. The related term developmental toxicity includes all manifestations of abnormal development that are caused by environmental insult. These may include growth retardation, delayed mental development or other congenital disorders without any structural malformations. Teratogens are substances that may cause birth defects via a toxic effect on an embryo or fetus. Known teratogens include: retinol, thalidomide, Mercury (element), mercury, Alcohol (drug), alcohol, lead, polychlorinated biphenyls (PCBs), and 2,3,7,8-tetrachlorodibenzodioxin. Etymology The term was borrowed in 1842 from the French , where it was formed in 1830 from the Greek language, Greek (word stem ), meaning "sign sent by the gods, portent, marvel, monster", and (''-ology''), used ...
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Metabolites
In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones). A primary metabolite is directly involved in normal "growth", development, and reproduction. Ethylene exemplifies a primary metabolite produced large-scale by industrial microbiology. A secondary metabolite is not directly involved in those processes, but usually has an important ecological function. Examples include antibiotics and pigments such as resins and terpenes etc. Some antibiotics use primary metabolites as precursors, such as actinomycin, which is created from the primary metabolite tryptophan. Some sugars are metabolites, such as fructose or glucose, which are both pre ...
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Thrombocytopenia
Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients and a third of surgical patients. A normal human platelet count ranges from 150,000 to 450,000 platelets/microliter (μl) of blood. Values outside this range do not necessarily indicate disease. One common definition of thrombocytopenia requiring emergency treatment is a platelet count below 50,000/μl. Thrombocytopenia can be contrasted with the conditions associated with an abnormally ''high'' level of platelets in the blood - thrombocythemia (when the cause is unknown), and thrombocytosis (when the cause is known). Signs and symptoms Thrombocytopenia usually has no symptoms and is picked up on a routine complete blood count. Some individuals with thrombocytopenia may experience external bleeding, such as nosebleeds or bleeding gums. S ...
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Peripheral Neuropathy
Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or organ function depending on which nerves are affected; in other words, neuropathy affecting motor, sensory, or autonomic nerves result in different symptoms. More than one type of nerve may be affected simultaneously. Peripheral neuropathy may be acute (with sudden onset, rapid progress) or chronic (symptoms begin subtly and progress slowly), and may be reversible or permanent. Common causes include systemic diseases (such as diabetes or leprosy), hyperglycemia-induced glycation, vitamin deficiency, medication (e.g., chemotherapy, or commonly prescribed antibiotics including metronidazole and the fluoroquinolone class of antibiotics (such as ciprofloxacin, levofloxacin, moxifloxacin)), traumatic injury, ischemia, radiation therapy, excessi ...
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Progression-free Survival
Progression-free survival (PFS) is "the length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse". In oncology, PFS usually refers to situations in which a tumor is present, as demonstrated by laboratory testing, radiologic testing, or clinically. Similarly, "disease-free survival" is the length of time after patients have received treatment and have no detectable disease. Time to progression (TTP) does not count patients who die from other causes but is otherwise a close equivalent to PFS (unless there are many such events). The FDA gives separate definitions and prefers PFS. Background PFS is widely used as a surrogate endpoint in oncology. The definition of "progression" generally involves imaging techniques (plain radiograms, CT scans, MRI, PET scans, ultrasounds) or other aspects: biochemical progression may be defined on the basis of an increase in a tumor marker (such as CA125 for epithelial ...
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Nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 definitions of nausea were proposed in a 2011 book on the topic. Nausea is a non-specific symptom, which means that it has many possible causes. Some common causes of nausea are gastroenteritis and other gastrointestinal disorders, food poisoning, motion sickness, dizziness, migraine, fainting, low blood sugar, anxiety, and lack of sleep. Nausea is a side effect of many medications including chemotherapy, or morning sickness in early pregnancy. Nausea may also be caused by disgust and depression. Medications taken to prevent and treat nausea and vomiting are called antiemetics. The most commonly prescribed antiemetics in the US are promethazine, metoclopramide, and the newer ondansetron. The word nausea is from Lat ...
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Peripheral Oedema
Peripheral edema is edema (accumulation of fluid causing swelling) in tissues perfused by the peripheral vascular system, usually in the lower limbs. In the most dependent parts of the body (those hanging distally), it may be called dependent edema. Cause The condition is commonly associated with vascular and cardiac changes associated with aging but can be caused by many other conditions, including congestive heart failure, kidney failure, liver cirrhosis, portal hypertension, trauma, alcoholism, altitude sickness, pregnancy, hypertension, sickle cell anemia, a compromised lymphatic system or merely long periods of time sitting or standing without moving. Some medicines (e.g. amlodipine, pregabalin) may also cause or worsen the condition. Prognosis Successful treatment depends on control of the underlying cause. Severe swelling can cause permanent damage to nerves, resulting in peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term de ...
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