Sorafenib, sold under the brand name Nexavar, is a

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

inhibitor drug approved for the treatment of primary kidney cancer (advanced

renal cell carcinoma Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, resp ...

), advanced primary liver cancer (

hepatocellular carcinoma Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide. It occurs in t ...

), FLT3-ITD positive AML and radioactive iodine resistant advanced thyroid carcinoma.

Mechanism of action

Sorafenib is a

protein kinase inhibitor A protein kinase inhibitor is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate, or PO4, group) to a protein and can modulate its function. The phospha ...

with activity against many

protein kinase A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a fu ...

s, including

VEGFR VEGF receptors are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Also, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR), depending on alternative splicing. Inh ...

PDGFR Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellu ...

and RAF kinases. Of the RAF kinases, sorafenib is more selective for

c-Raf RAF proto-oncogene serine/threonine-protein kinase, also known as proto-oncogene c-RAF or simply c-Raf or even Raf-1, is an enzyme that in humans is encoded by the ''RAF1'' gene. The c-Raf protein is part of the ERK1/2 pathway as a MAP kinase ( ...

than B-RAF. (See BRAF (gene)#Sorafenib for details the drug's interaction with B-Raf.) Sorafenib treatment induces

autophagy Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...

, which may suppress tumor growth. Based on its 1,3-disubstituted urea structure, sorafenib is also a potent

soluble epoxide hydrolase Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that in humans is encoded by the EPHX2 gene. sEH is a member of the epoxide hydrolase family. This enzyme, found in both the cytosol and peroxisomes, binds to specific epoxides and converts ...

inhibitor and this activity likely reduces the severity of its adverse effects.

Medical uses

Sorafenib is indicated as a treatment for advanced

(RCC), unresectable

s (HCC) and

thyroid cancer Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...

Kidney cancer

Clinical trial results, published January 2007, showed that, compared with placebo, treatment with sorafenib prolongs

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 p ...

in patients with advanced clear cell renal cell carcinoma in whom previous therapy has failed. The median progression-free survival was 5.5 months in the sorafenib group and 2.8 months in the placebo group (

hazard ratio In survival analysis, the hazard ratio (HR) is the ratio of the hazard rates corresponding to the conditions characterised by two distinct levels of a treatment variable of interest. For example, in a clinical study of a drug, the treated populati ...

for disease progression in the sorafenib group, 0.44; 95% confidence interval I 0.35 to 0.55; P<0.01). In Australia this is one of two TGA-labelled indications for sorafenib, although it is not listed on the

Pharmaceutical Benefits Scheme The Pharmaceutical Benefits Scheme (PBS) is a program of the Australian Government that subsidises prescription medication for Australian citizens and permanent residents, as well as international visitors covered by a reciprocal health care ag ...

for this indication.

Liver cancer

At ASCO 2007, results from the SHARP trial were presented, which showed efficacy of sorafenib in

. The primary endpoint was median

overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...

, which showed a 44% improvement in patients who received sorafenib compared to placebo (

0.69; 95% CI, 0.55 to 0.87; p=0.0001). Both median survival and time to progression showed 3-month improvements; however, there was no significant difference in median time to symptomatic progression (''p''=0.77). There was no difference in quality of life measures, possibly attributable to toxicity of sorafenib or symptoms related to underlying progression of liver disease. Of note, this trial only included patients with Child-Pugh Class A (i.e. mildest) cirrhosis. Because of this trial sorafenib obtained FDA approval for the treatment of advanced hepatocellular carcinoma in November 2007. In a randomized, double-blind, phase II trial combining sorafenib with

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used togeth ...

, the median time to progression was not significantly delayed compared with doxorubicin alone in patients with advanced hepatocellular carcinoma. Median durations of overall survival and

were significantly longer in patients receiving sorafenib plus doxorubicin than in those receiving doxorubicin alone. A prospective single-centre phase II study which included the patients with unresectable hepatocellular carcinoma (HCC) concluding that the combination of sorafenib and DEB- TACE in patients with unresectable HCC is well tolerated and safe, with most toxicities related to sorafenib. In Australia this is the only indication for which sorafenib is listed on the

PBS The Public Broadcasting Service (PBS) is an American public broadcasting, public broadcaster and Non-commercial activity, non-commercial, Terrestrial television, free-to-air television network based in Arlington, Virginia. PBS is a publicly fu ...

and hence the only government-subsidised indication for sorafenib. Along with renal cell carcinoma, hepatocellular carcinoma is one of the TGA-labelled indications for sorafenib.

Thyroid cancer

On 22 November 2013, sorafenib was approved by the FDA for the treatment of locally recurrent or metastatic, progressive differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment. The phase III DECISION trial showed significant improvement in progression-free survival but not in overall survival. However, as is known, the side effects were very frequent, specially hand and foot skin reaction.

Adverse effects

Adverse effects by frequency
''Note: Potentially serious side effects are in bold.''
Very common (>10% frequency)
*

Lymphopenia Lymphocytopenia is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. It is also called lymphopenia. The opposite is lymphocytosis, which re ...

Hypophosphataemia Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening ...

Low blood

phosphate In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid . The phosphate or orthophosphate ion is derived from phospho ...

levels *

Haemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagi ...

Bleeding; including serious bleeds such as intracranial and intrapulmonary bleeds *

Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

High blood pressure * Diarrhea * Rash *

Alopecia Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...

(hair loss; occurs in roughly 30% of patients receiving sorafenib) *

Hand-foot syndrome Chemotherapy-induced acral erythema, also known as palmar-plantar erythrodysesthesia or hand-foot syndrome is reddening, swelling, numbness and desquamation (skin sloughing or peeling) on palms of the hands and soles of the feet (and, occasionally ...

Pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

(itchiness) *

Erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not assoc ...

* Increased

amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...

* Increased

lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...

* Fatigue * PainIncluding abdominal pain, headache, tumour pain, etc. * Nausea * VomitingConsidered a low (~10-30%) risk chemotherapeutic agent for causing emesis) Common (1-10% frequency)
*

Leucopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

Low level of

white blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...

s in the blood * NeutropoeniaLow level of

neutrophils Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying in ...

in the blood *

Anaemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

Low level of

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s in the blood *

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 an ...

Low level of

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B lymphocytes and secrete large quantities of proteins called antibodies in response to being presented specific substan ...

s in the blood *

Anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

(weight loss) *

Hypocalcaemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mmol ...

Low blood

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

Hypokalaemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abnor ...

Low blood

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosphe ...

* Depression * Peripheral sensory neuropathy *

Tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...

Hearing ringing in the ears *

Congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

Myocardial infarction A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...

Heart attack *

Myocardial ischaemia Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic pla ...

Lack of blood supply for the heart muscle * Hoarseness * Constipation *

Stomatitis Stomatitis is inflammation of the mouth and lips. It refers to any inflammatory process affecting the mucous membranes of the mouth and lips, with or without oral ulceration. In its widest meaning, stomatitis can have a multitude of different cau ...

Mouth swelling, also dry mouth and

glossodynia Burning mouth syndrome (BMS) is a burning, tingling or scalding sensation in the mouth, lasting for at least four to six months, with no underlying known dental or medical cause. No related medical sign, signs of disease are found in the mouth. ...

Dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier t ...

Indigestion *

Dysphagia Dysphagia is difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, in some contexts it is classified as a disease#Terminology, condition in its own right. It may be a sensation that suggests difficulty in the passag ...

Not being able to swallow * Dry skin * Exfoliative dermatitis *

Acne Acne, also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, black ...

* Skin desquamation *

Arthralgia Arthralgia (from Greek ''arthro-'', joint + ''-algos'', pain) literally means ''joint pain''. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication. According to MeSH, ...

Sore joints *

Myalgia Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

Muscle aches *

Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

Kidney failure *

Proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy (although this symptom ma ...

Excreting protein sually plasma proteinsin the urine. Not dangerous in itself but it is indicative kidney damage *

Erectile dysfunction Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men.Cunningham GR, Rosen RC. Overview of male ...

Asthenia Weakness is a symptom of a number of different conditions. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a variety of skeletal muscle diseases, i ...

(weakness) * Fever * Influenza-like illness * Transient increase in transaminase Uncommon (0.1-1% frequency)
*

Folliculitis Folliculitis is the infection and inflammation of one or more hair follicles. The condition may occur anywhere on hair-covered skin. The rash may appear as pimples that come to white tips on the face, chest, back, arms, legs, buttocks, or head. A ...

* Infection * Hypersensitivity reactionsIncluding skin reactions and

urticaria Hives, also known as urticaria, is a kind of skin rash with red, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and does not leave any long-lasti ...

(hives) *

Hypothyroidism Hypothyroidism (also called ''underactive thyroid'', ''low thyroid'' or ''hypothyreosis'') is a disorder of the endocrine system in which the thyroid gland does not produce enough thyroid hormone. It can cause a number of symptoms, such as po ...

Underactive thyroid *

Hyperthyroidism Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...

Overactive thyroid * HyponatraemiaLow blood sodium * Dehydration * Reversible posterior

leukoencephalopathy Leukoencephalopathy (leukodystrophy-like diseases) is a term that describes all of the brain white matter diseases, whether their molecular cause is known or unknown. It can refer specifically to any of these diseases: * Progressive multifocal leuk ...

Hypertensive crisis Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 120—sometimes termed malignant or accelerated hypertension) is referred to as a hypertensive crisis, as blood pressure at this level confers a high risk ...

Rhinorrhoea Rhinorrhea, rhinorrhoea, or informally runny nose is the free discharge of a thin mucus fluid from the nose; it is a common condition. It is a common symptom of allergies (hay fever) or certain viral infections, such as the common cold or COVID-1 ...

Runny nose * Interstitial lung disease-like events

Pneumonitis Pneumonitis describes general inflammation of lung tissue. Possible causative agents include radiation therapy of the chest, exposure to medications used during chemo-therapy, the inhalation of debris (e.g., animal dander), aspiration, herbicide ...

, radiation pneumonitis, acute respiratory distress, etc. *

Gastro-oesophageal reflux disease Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

(GORD) *

Pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormones. There are two main types: acute pancreatitis, and chronic pancr ...

Swelling of the

pancreas The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...

Gastritis Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possi ...

Swelling of the

stomach The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...

* Gastrointestinal perforationsFormation of a hole in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organ (biology), organs of the digestive syste ...

, leading to potentially fatal bleeds * Increase in

bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

leading, potentially, to

jaundice Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme meta ...

Yellowing of the skin and eyes due to a failure of the liver to adequately cope with the amount of bilirubin produced by the day-to-day actions of the body *

Cholecystitis Cholecystitis is inflammation of the gallbladder. Symptoms include right upper abdominal pain, pain in the right shoulder, nausea, vomiting, and occasionally fever. Often gallbladder attacks (biliary colic) precede acute cholecystitis. The pain l ...

Swelling of the

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath the liver, although ...

* CholangitisSwelling of the

bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

Eczema Dermatitis is inflammation of the Human skin, skin, typically characterized by itchiness, erythema, redness and a rash. In cases of short duration, there may be small blisters, while in long-term cases the skin may become lichenification, thick ...

Erythema multiforme Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands. It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...

A potentially fatal skin reaction *

Keratoacanthoma Keratoacanthoma (KA) is a common low-grade (unlikely to metastasize or invade) rapidly-growing skin tumour that is believed to originate from the hair follicle (pilosebaceous unit) and can resemble squamous cell carcinoma. The defining characteris ...

A fairly benign form of skin cancer *

Squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...

Gynaecomastia Gynecomastia (also spelled gynaecomastia) is the abnormal non-cancerous enlargement of one or both breasts in males due to the growth of breast tissue as a result of a hormone imbalance between estrogens and androgens. Updated by Brent Wisse (1 ...

(swelling of the breast tissue in men) * Transient increase in blood alkaline phosphatase * INR abnormal *

Prothrombin Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma- ...

level abnormal * bulbous skin reaction Rare (0.01-0.1% frequency) *

QT interval The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken ...

prolongationA potentially fatal abnormality in the electrical activity of the heart *

Angiooedema Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which a ...

Swelling of the skin and mucous membranes *

Anaphylactic reaction Anaphylaxis is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of use of emergency medication on site. It typically causes more than one of the follo ...

A potentially fatal allergic reaction *

Hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

Swelling of the liver * Radiation recall dermatitis *

Stevens–Johnson syndrome Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...

Leucocytoclastic vasculitis Cutaneous small-vessel vasculitis (CSVV), also known as hypersensitivity vasculitis, cutaneous leukocytoclastic vasculitis, hypersensitivity angiitis, cutaneous leukocytoclastic angiitis, cutaneous necrotizing vasculitis and cutaneous necrotizing v ...

Toxic epidermal necrolysis Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...

Nephrotic syndrome Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy ...

Rhabdomyolysis Rhabdomyolysis (also called rhabdo) is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of th ...

The rapid breakdown of muscle tissue leading to the build-up of

myoglobin Myoglobin (symbol Mb or MB) is an iron- and oxygen-binding protein found in the cardiac and skeletal muscle tissue of vertebrates in general and in almost all mammals. Myoglobin is distantly related to hemoglobin. Compared to hemoglobin, myoglobi ...

in the blood and resulting in damage to the kidneys

History

Renal cancer

Sorafenib was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) in December 2005, and received

European Commission The European Commission (EC) is the executive of the European Union (EU). It operates as a cabinet government, with 27 members of the Commission (informally known as "Commissioners") headed by a President. It includes an administrative body o ...

marketing authorization in July 2006,

– Enterprise and industry
Nexavar
. Retrieved 24 April 2007. both for use in the treatment of advanced renal cancer.

Liver cancer

The European Commission granted marketing authorization to the drug for the treatment of patients with

(HCC), the most common form of liver cancer, in October 2007, and FDA approval for this indication followed in November 2007. In November 2009, the UK's

National Institute of Clinical Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...

declined to approve the drug for use within the

NHS The National Health Service (NHS) is the umbrella term for the publicly funded healthcare systems of the United Kingdom (UK). Since 1948, they have been funded out of general taxation. There are three systems which are referred to using the " ...

in England, Wales and Northern Ireland, stating that its effectiveness (increasing survival in primary liver cancer by 6 months) did not justify its high price, at up to £3000 per patient per month. In Scotland the drug had already been refused authorization by the

Scottish Medicines Consortium Healthcare Improvement Scotland (HIS) is the national healthcare improvement organisation for Scotland. It is a public body which is part of the Scottish National Health Service, created in April 2011. History NHS Quality Improvement Scotland ( ...

for use within

NHS Scotland NHS Scotland, sometimes styled NHSScotland, is the publicly funded healthcare system in Scotland and one of the four systems that make up the National Health Service in the United Kingdom. It operates 14 territorial NHS boards across Scotland, ...

, for the same reason. In March 2012, the Indian Patent Office granted a domestic company,

Natco Pharma Natco Pharma is an Indian multinational pharmaceutical company based in Hyderabad. The company manufactures finished dosage formulations active pharmaceutical ingredients and crop health science products, and also provides contract manufacturin ...

, a license to manufacture generic sorafenib, bringing its price down by 97%. Bayer sells a month's supply, 120 tablets, of Nexavar for. Natco Pharma will sell 120 tablets for , while still paying a 6% royalty to Bayer. The royalty was later raised to 7% on appeal by Bayer. Under the Patents Act, 1970 and the World Trade Organisation TRIPS Agreement, the government can issue a

compulsory license A compulsory license provides that the owner of a patent or copyright licenses the use of their rights against payment either set by law or determined through some form of adjudication or arbitration. In essence, under a compulsory license, an i ...

when a drug is not available at an affordable price.

Society and culture

Nexavar controversy

In January 2014, Bayer's CEO

Marijn Dekkers Marijn Emmanuel Dekkers (born 22 September 1957 in Tilburg, Netherlands) is a Dutch-American former pharmaceutical businessman. He was CEO of Bayer AG from 2010 to 2016. He served as CEO of Thermo Fisher Scientific Inc. from 2002 to 2009. He served ...

allegedly stated that Nexavar was developed for "Western patients who can afford it, not for Indians". However, Dekkers actually never said this. In fact, his words were misquoted and the context was omitted. A kidney cancer patient would pay $96,000 (£58,000) for a year's course of the Bayer-made drug, whereas the cost of the Indian version of the

generic drug A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

would be around $2,800 (£1,700).

Research

Lung

In some kinds of lung cancer (with squamous-cell histology) sorafenib administered in addition to

paclitaxel Paclitaxel (PTX), sold under the brand name Taxol among others, is a chemotherapy medication used to treat a number of types of cancer. This includes ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer ...

and

carboplatin Carboplatin, sold under the trade name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is used b ...

may be ''detrimental'' to patients.

Ovarian cancer

Sorafenib has been studied as maintenance therapy after ovarian cancer treatment and in combination with chemotherapy for recurrent ovarian cancer but did not show results that led to approval of the drug for these indications.

Brain (recurrent glioblastoma)

There is a phase I/II study at the Mayo Clinic of sorafenib and CCI-779 (

temsirolimus Temsirolimus, sold under the brand name Torisel, is an intravenous drug for the treatment of renal cell carcinoma (RCC), developed by Wyeth Pharmaceuticals and approved by the U.S. Food and Drug Administration (FDA) in May 2007, and was also appro ...

) for recurrent

glioblastoma Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...

Desmoid tumor (aggressive fibromatosis)

A study performed in 2008 showed that Sorafenib is active against

aggressive fibromatosis Aggressive fibromatosis or desmoid tumor is a rare condition. Desmoid tumors arise from cells called fibroblasts, which are found throughout the body and provide structural support, protection to the vital organs, and play a critical role in wou ...

. This study is being used as justification for using sorafenib as an initial course of treatment in some patients with

. A phase III clinical trial is testing the effectiveness of sorafenib to treat desmoid tumors (also known as

), after positive results in the first two trial stages. Dosage is typically half of that applied for malignant cancers (400 mg vs 800 mg). NCI are sponsoring this trial.

Notes

References

External links

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