User:Fuse809/sandbox3

Note: Bold typeface is used to put emphasis on key terms. To make it easier to navigate this page I have hidden the tables as they are massive. When I start talking about how common each cancer is amongst the different races I am referring to the country of origin of the affected. For instance, a white Australian would in this system be called European, likewise a white American would be called European and an African American would be an African.

Blood cancers are among the most common forms of cancers with around 31 Australians diagnosed with one per day (or around 11,300 diagnosed per year) and they include: lymphomas, leukaemias and multiple myeloma (MM).^[1] Many are very treatable if caught early, although, as always there's always the odd exception and, of course, the later it's caught the worse the outcome. Lymphomas are cancers of the cells (lymphocytes; the chief cells of adaptive immune system) found in lymphatic system including lymph nodes, spleen, bone marrow (the centre of bones where blood cells are created), etc. Lymphomas can be broken up into two major categories, Hodgkin lymphoma (formerly known as Hodgkin's disease or HL) and non-Hodgkin lymphoma (NHL). Leukaemias can be broken up into two main categories: acute and chronic. The distinction is that acute leukaemias are more rapidly progressing than their chronic counterparts. They are the most common variety in children. Leukaemias can also be broken up into a further two major categories: lymphoblastic (or lymphoid/lymphocytic) and myeloid (or myelogenous) types in most cases. Lymphoblastic varieties arise from lymphoblasts which are produced in the bone marrow and mature (i.e. develop into) into lymphocytes. Myeloid leukaemia subtypes arise from myeloid cells which are precursors to myelocytes, a type of white blood cell which make up the innate immune system. Multiple myeloma is a cancer of the plasma cells (mature B-lymphocytes that produce antibodies to defend our body from past invaders).

Now I understand some of us don't want to read about the drugs and just get down to the bottom line and the basics of this article. Because of this I have created a table on the drugs and how they work so you can refer back to them if you want more details.

Chemotherapy-Induced Nausea and Vomiting

Before I go any further I should mention that oncologists (cancer docs) can be rather effective at helping cancer patients cope with the side effects of chemotherapy, including emesis [vomiting] and as part of this they treat patients with antiemetic [nausea and vomiting-inhibiting and -preventing] drugs usually before they're subjected to highly emetogenic chemotherapy. Such drugs include aprepitant (EMEND; very expensive at ~$40 AUD/pill, covered by the PBS as a treatment for Chemotherapy-Induced Nausea and Vomiting [CINV], however. It works by antagonising (blocking) the neurokinin 1 (NK₁) receptor in the chemoreceptor trigger zone [CTZ], a part of the brain that contains a heap of chemoreceptors which are receptors that respond to certain chemicals, mostly toxic chemicals, and, in response to this sort of stimuli, activates the gag reflex and hence induces nausea and vomiting^[2]), ondansetron (ZOFRAN; blocks the serotonin 5-HT₃ receptors found in the CTZ and digestive tract [specifically on the vagus nerve (a large nerve that goes from the brain down through the torso into the digestive tract) for the most part]^[2]) and dexamethasone (another corticosteroid; much more potent than other corticosteroids. It assists antiemetic drugs in suppressing emesis but also stimulates appetite).^[3]

Note: All estimates as to the incidence of nausea and vomiting as side effects of chemotherapy assume that the patient hasn't received the preventative regimen listen listed in this section.

Acronyms & Other terms

Definitions

Term Definition Drug terms Alkylating agent Substances that add an alkyl (CnH2n+1) group to DNA. This causes a problem because cancer cells tend to correct errors in their DNA less robustly than healthy cells and they more eagerly reproduce. Rapidly reproducing cells like cancer cells tend to be greater affected by alkylating agents because they inhibit cell division as cells can't divide with faulty (such as alkylated) DNA. These were the very first class of anticancer agents, as this class includes the nitrogen mustards (mustard gas analogues) that were initially tested based on the observation that rapidly-dividing cells like the blood and gastrointestinal cells were most affected by the mustard gases of WWI. Hence since it was known that cancer cells divided rapidly and this was one of the defining features of malignancies it was decided to test a lower dose of nitrogen mustards in terminal patients with non-hodgkin's lymphoma (NHL). Although before you start calling these docs akin to Nazi scientists, they did perform animal tests before they decided to test it on humans. Antimetabolites Substances that inhibit natural biosynthetic pathways in the body. Antifolate, folate antagonist or inhibitors work by inhibiting the enzyme DHFR. This enzyme is used to create THF from DHF, hence DHFR inhibitors produce a folate deficiency in affected cells. Folate deficiency leads to the halting of cell division. Purine and pyrimidine analogues tend to act by taking on the role of the purines/pyrimidines found in DNA (guanine, adenine, thymine and cytosine) and by switching these bases for itself. Antineoplastic Anticancer. Ataxia Incoordination. Lacking coordination in one's movements. Cytotoxicity Cell toxicity. Many chemotherapeutics are so called "cytotoxic" because they either kill off cells directly (including healthy cells) or they kill them indirectly by preventing them from reproducing to replace any cells that die as part of the usual ageing process of cells. Diabetic ketoacidosis An accumulation of acidic ketone bodies in the blood that results from the inability of the body to utilise the sugar (glucose) in the blood. This can be solely drug-induced, but other cases it can be due to untreated diabetes mellitus. Emetogenic Emesis (vomiting)-inducing. EPSE Extrapyramidal side effects. Movement side effects like tremor, muscle rigidity, changes in gait (of one's walk), involuntary muscle movements, etc. IM Intramuscular injection. An injection directly into the muscle tissue, most common sites of these injections are in the upper arm, the upper leg, the butt and the stomach. IV Intravenous injection. An injection into the veins most often in the wrist or on the other side of the elbow. Monoclonal antibodies In terms of drugs these are drugs that are designed to bind to target cells and, by so doing, make them a target of the body's immune response. Nitrogen mustard A class of mustard gas analogues. See alkylating agent for mechanism of action PO Per os; oral administration of the drug in question. Proteasome inhibitor Proteasomes are a compartment of cells that breakdown proteins, like receptors or enzymes, so that new proteins can be created from the amino acids that were in said broken down proteins. Some of the proteins broken down by the proteasome of say cancer cells are pro-apoptotic factors which, if they're left intact due to say this drug inhibiting the action of the proteasome, may accumulate and induce cell apoptosis.[4] ROM Route(s) of administration. The way a drug is delivered. SC Subcutaneous injection, under the skin. Semisynthesis These substances are synthesised via reactions involving natural compounds. SL Sublingually administered, that is, under the tongue. TD Transdermally administered, that is, via a patch on the skin. Tyrosine kinase inhibitor Drugs that inhibit tyrosine kinase. Some receptors, most commonly expressed on the surface of cells, activate tyrosine kinases in order to elicit their physiologic effects. Tyrosine kinases are implicated in survival, angiogenesis, proliferation and invasion of cancers into the tissues (this is in the case of solid tumours, not blood cancers). Vinca alkaloids Substances either derived from the Rosy Periwinkle plant or synthesised from compounds that are. They inhibit the formation of microtubules which are used during cell division. Hence the vinca alkaloids inhibit cell division. Biomedical terms Adaptive immune system That is, the part of the immune system that adapts its attack or response according to the different invaders threatening the body. Addison's disease A disease state in of which the adrenal glands on top of the kidneys seize to function correctly, leading to a deficiency of the corticosteroid hormones that are produced by the organs. Alopecia Hair loss. ALP Alkaline phosphatase, an enzyme that helps with the removal of a phosphate group from substances such as proteins, fats and nucleic acids (the building blocks of DNA and RNA). One role for these enzymes would probably be in removing phosphate groups from phospholipids, the building blocks of the outer layer of cells, the so called phospholipid cell membrane. Amenorrhoea The absence or cessation of menstrual cycles in women. Amylase An enzyme found in the saliva and in the digestive tract, it breaks down starch and turns it into glucose (a sugar). Anaphylaxis A life-threatening allergic reaction. Angiogenesis The formation of new blood vessels, this process can be exploited by cancers to feed their growth and spread. Apoptosis Programmed cell death. This is basically designed to prevent cells from mutating or otherwise becoming a problem. Arrhythmias Abnormal heart rhythms. Arthralgia Joint pain. AST Aspartate transaminase, an enzyme found in various organs. The levels in the blood are often used as indicators of liver function with higher levels usually corresponding to a reduction in liver function. Azoospermia Basically when the number of sperm in a man's semen is so low it is undetectable. BBB Blood-brain barrier. The protective layer of cells that separate the blood in the brain and spinal cord and the blood in the periphery (outside the brain and spinal cord). Bilirubin A yellow breakdown product of the breakdown of haem. Haem is an iron compound used to make haemoglobin (the protein in red blood cell that carries oxygen from the lungs to the tissues of the body). It is normally excreted the liver in bile, and some of it gets converted into urolibin and excreted by the kidneys in the urine. It is responsible for the brown colour of faeces, the yellow colour of urine. In cases of liver disease it is responsible for their yellow skin and eyes. Bradycardia Low heart rate. Candidiasis A fungal infection that's better known as thrush. Carcinogen Cancer-causing substances. Examples include alcohol, tobacco, arsenic, tar, etc. Cardiotoxicity Damage to the heart. Sometimes cardiotoxicity is a temporary complication of chemotherapy, other timesmil it can be permanent. Cell division The replication of cells. This is essential as our cells have a limited lifetime. Chemotherapy-induced acral erythema A constellation of skin reactions to chemotherapy, they most commonly occur on the palms of the hands and the soles of the feed. Includes desquamation (skin pealing off), numbness, swelling and reddening of the skin. CNS Central nervous system. The brain and spinal cord. The adjective "central" usually refers to the central nervous system. Contusion Bruising. Cutaneous Pertaining to the skin. Cytokine Proteins produced by the immune system as part of its assault on invaders. Some induce inflammation, others relieve it and while others alter immune function. Tumour necrosis factor alpha (TNF-α) and interleukin-2 are examples of pro-inflammatory cytokines. Dermatology Pertaining to skin. DHFR Dihydrofolate reductase. An enzyme that catalyses the synthesis of tetrahydrofolate (THF) from dihydrofolate. Differentiation syndrome A common complication of treatment in those with APL. Tretinoin and arsenic trioxide are the usual precipitating treatments for this reaction. It is characterised by: dyspnoea, fever, weight gain, peripheral oedema, hypotension, acute renal failure, heart failure, pleural and pericardial effusion and pulmonary infiltrates. These signs usually occur within the first few weeks of treatment. Leucocytosis often occurs concurrently, although it doesn't always. Concurrent chemotherapy may reduce the incidence. Benefits of prophylactic corticosteroids are not proven. DNA Deoxyribonucleic acid. The base unit of life. DNA replication is an essential step in cell division. DNA methyltransferase An enzyme that methylates DNA. This changes gene expression, that is, the generation of proteins in order for cells to utilise the abilities that their genes enable them to have. Different cells express different genes and hence produce different proteins. Dyspnoea Shortness of breath. ECG Electrocardiogram. This is basically where doctors or nurses take measurements of the patient's heart electrical activity and study said activity. It usually produces a graph like this: . Erythema Superficial reddening of the skin, usually in patches, as a result of injury or irritation causing dilatation of the blood capillaries. Exertional dyspnoea Shortness of breath that's triggered by physical activity, less than would normally be required to cause dyspnoea. GI Gastrointestinal tract, also known as the digestive tract. The parts of the body that takes the nutrients from our food. Gingival haemorrhage Bleeding from the gums. Gynaecomastia Swelling of the breast tissue in men. Haematologic malignancy Synonym for blood cancer. Haematuria Blood in the urine. Haemolysis Breakdown of red blood cells. Haemolytic uraemic syndrome A condition where the red blood cells breakdown and is accompanied by kidney dysfunction, potentially causing kidney damage and failure. Haemorrhage Bleeding. Haemorrhagic conjunctivitis Bleeding into the eyes. Haemorrhagic cystitis Bleeding into the bladder. Hepatotoxicity Liver damage. Name comes from the fact that the liver cells are called hepatocytes. HTN Hypertension. High blood pressure. Hypercalcaemia High blood calcium level. Hyperglycaemia High blood sugar. Hyperkalaemia High blood potassium level. Hyperphosphataemia High blood levels of phosphate. Hyperpigmentation When the skin goes brown or black due to an abnormal level of skin pigments (the pigments that give our skin its colour; the darker your skin the more the pigments) Hyperuricaemia High blood levels of uric acid. Uric acid is the final by product of purine metabolism in humans. Hyperuricaemia can lead to the following symptoms: gout (periodic pain and swelling of the joints) and uric acid nephrolithiasis which is a kidney problem that leads to blood in the urine, pain in the lower back originating from where the kidneys are, abdominal pain and nausea/vomiting. Hypomagnesia Low blood levels of the essential nutrient, magnesium. Hyponatraemia Low blood sodium levels. Hypotension Low blood pressure. Innate immune system The first line defence of the body against invaders that pretty much treats all invaders the same (only real distinction they make is between the class of invader; like for instance it treats bacteria, viruses and parasites differently) because of the fact it doesn't really adapt (as in the case of the adaptive immune response) how it responds for the specific invader Interstitial pneumonia Progressive scarring of both lungs. Leucopenia Low WBC. This leaves people wide open to infections; if it's severe enough it can be fatal. Leucocytosis High WBC. Lipase An enzyme that breaks down fats. Malignancy Synonym for cancer. MI Myocardial infarction, better known as a heart attack. This is when the blood flow to the heart muscle is temporarily obstructed. Mucositis The painful swelling or ulceration of the mucous membrane lining of the gastrointestinal tract. Myalgia Muscular aches. Myelosuppression Suppression of the formation of new blood cells by the bone marrow. This can lead to anaemia (low red blood cell count) and leucopenia. Myocardial ischaemia When the blood flow to the heart muscle is obstructed, usually longer-term and less severely than a MI. Neoplasm Cancer. Nephrotoxicity Kidney damage. The kidneys are very sensitive to harm and hence any kidney damage done by drugs is likely to be permanent. Nucleobase (In the context of human medicine) A nitrogenous (i.e. contains nitrogen atoms) compound, of either the purine or pyrimidine class. Examples are guanine, thymine, cytosine and adenine. Nucleoside Base components of DNA and RNA. Inside nucleosides is a sugar and a nucleobase which are one of the purines or pyrimidines. The sugar is either ribose (RNA) or deoxyribose (DNA). Cytidine is cytosine combined with ribose. Adenosine is cytosine combined with ribose. Thymidine is thymine combined with deoxyribose. Guanosine is guanine combined with ribose. Neutropaenia Low neutrophil count. This increases one's susceptibility to bacterial infections. Neutrophil Neutrophils are the cells of the innate immune system that deal with bacteria. Oedema A condition characterized by an excess of watery fluid collecting in the cavities or tissues of the body. Oesophagitis Swelling of the oesophagus - the tube that connects the stomach with the mouth. Oligospermia Low sperm count in a man's semen. Orthostatic hypotension A drop in blood pressure that occurs upon standing, and if it's severe enough it can cause people to faint upon getting up. Ototoxocity Damage to the hearing. Can be either reversible or irreversible. Pancytopaenia A drop in the number of all varieties of blood cells. Perforation The formation of a hole in the affected organ, or skin. e.g. GI perforation is when a hole forms in the GI tract. Pericardial effusion Fluid accumulating in the sac that encloses the heart. Pericarditis Swelling of the sac enclosing the heart. Peripheral neuropathy This is basically when somebodies nerves become damaged causing a wide variety of different symptoms. Peripheral sensory neuropathy (PSN) is when this damage is confined to the nerves of the body that send sensory signals containing information pertaining to our sense of touch to our brain. PSN often results in false feelings of pain, hot or cold, numbness, itching, pins and needles, etc. Petechiae Small bleeds that occur underneath the skin that lead to red spots appearing. Pleural effusion The filling of the lungs with fluid, most often blood. Pneumonitis Inflammation of the air sacs (alveoli) of the lungs. PNS Peripheral nervous system, the nerves found outside the brain. These nerves usually control the muscles or relay sensory information to the brain. The adjectives "peripheral" and "periphery" usually refer to the parts of the body outside the brain and spinal cord. Purine A class of compounds that includes guanine and adenine — two of the building blocks of DNA. Adenine is also a precursor to adenosine. Adenosine has numerous functions in the body. For one, it is an extracellular chemical messenger in the body (i.e. it conveys messages between cells and organ systems), where it acts on the adenosine receptors and produces sedating, calming and blood pressure-lowering effects. Caffeine works it magic by inhibiting the actions of adenosine. Adenosine is also a component of adenosine triphosphate (ATP) — the energy currency of our cells. Cyclic adenosine monophosphate (cAMP) is a intracellular (i.e. it acts as a messenger between the various components of the cell) signalling molecule made of adenosine too. Cyclic guanine monophosphate (cGMP) is another intracellular signalling molecule. If you want to see some of its roles look at somebody that just took a phosphodiesterase 5 (PDE5) inhibitor like sildenafil (Viagra) or tadalafil (Cialis), which increase the intracellular level of cGMP in a number of cells. Pyrimidine A class of compounds that includes thymine and cytosine — two of the building blocks of DNA. QT interval A measurement made using the ECG graph. If this measurement is abnormally large (i.e. the QT interval is prolonged) it can indicate potentially fatal changes in heart activity which could lead to dangerous arrhythmias (heart rhythms). One such abnormal heart rhythm is torsades de pointes which can be fatal. Radiodermatitis Swelling of the skin at the site of radiation exposure (such as for the radiotherapy of cancer). Rhabdomyolysis The breakdown of muscle tissue leading to the build-up of myoglobin in the blood leading to kidney damage and even failure. Ribonucleotide The base units of RNA, and by means of an enzyme ribonucleotide reductase it can also be turned into deoxynucleotides, the building blocks of DNA. Secondary malignancy A cancer that occurs as a result of chemotherapy treatment. Sepsis A blood infection that kills about half of those that get it. SIADH Syndrome of inappropriate secretion of antidiuretic hormone (ADH). ADH is a hormone that regulates the retention of water in the body. Higher the level of ADH, the less water in the urine secreted. SIADH results from an inappropriate release of ADH causing an abnormal level of water retention leading to electrolyte abnormalities like hyponatraemia, etc. SIADH is a life-threatening condition and is often the cause of death in those abusing MDMA (ecstasy). Stevens-Johnson syndrome (SJS) A less severe, but still often life-threatening form of TEN. THF The active form of folate (folic acid; the essential vitamin). This substance is used in the synthesis of DNA and RNA. Thrombocytopaenia Low platelet count. Platelets are the cells of the blood involved in blood clotting, such as to stop bleeding from wounds or bleeding into bruises (bruises are bleeds under the skin). This increases one's susceptibility to bleeds and bruising. Thrombophlebitis Swelling of the tissues surrounding a blood clot. Topoisomerase II An enzyme that's involved in DNA synthesis during cell division. Toxic epidermal necrolysis (TEN) A potentially fatal skin reaction where the layers of the skin separate leading to the sloffing off of one's skin. Vagus nerve A nerve the runs down from the brain through the neck into the torso, including many of the vital organs found in the torso, such as the gastrointestinal (digestive) tract. Vasculitis The destruction of blood vessels by means of inflammation (swelling). WBC White blood cells count; white blood cells are the cells of the immune system, that defend the body from invaders and cancer. Government/Beaurocratic/Miscellaneous other terms AMH Australian Medicines Handbook. Unless otherwise specified the version I'm using is the 2013 edition. This is a book Australian quacks and pharmacists use to guide prescribing decisions.[5] BNF British National Formulary (BNF). Unless otherwise specified I'm using the 65th edition (BNF 65).[6] The UK version of the AMH. FDA Food and Drug Administration. The US's regulatory administration on food and drugs. Est. on 30th June 1906. MHRA Medicines and Healthcare Products Regulatory Agency. The UK's regulatory administration on therapeutic products. Est. in 2003 from the merger of two UK gov. agencies, Medicines Control Agency (MCA) and Medical Devices Agency (MDA). NICE National Institute for Health and Care Excellence. A UK institute that regularly gives out clinical guidelines for the use of drugs and clinical care. PBS Pharmaceutical Benefits Scheme. The Australian government's scheme to subsidise us Aussies meds. The usual max price of prescriptions when they're subsidised by the PBS is $36.10 AUD. Although it can less than this for those on pensions. TGA Therapeutic Goods Administration. The Australian regulatory administration on drugs. Est. in 1989, although drugs started to be approved by the TGA in 1991.

Drugs used in the management of blood cancers

Note: Unless otherwise specified Very common means that the side effect in question occurs in 10% or more of patients treated with said drug. Common means that the side effect occurs in 1-10% of patients treated with said drug. Uncommon means that the side effect occurs in 0.1-1% of patients treated with the drug. Rare means that the side effect occurs in <0.1% patients treated with the drug.

Antineoplastics

Name (brand name(s)) PBS? [Note 1] Drug class[Note 2] Mechanism of action Source Chemical structure Date of TGA approval [Note 3] Date of FDA approval ROM Side effects Cytotoxic antineoplastics Azacitidine (Vidaza) N Antimetabolite Cytidine analogue and DNA methyltransferase inhibitor Synthetic 30 November 2009 19 May 2004 SC Very common: arthralgia, headache, weight loss, pain in limb, pharyngitis, contusion, oedema, back pain, dizziness, erythema, chest pain, nose bleed, muscle pain, abdominal pain, pallor, nasopharyngitis, skin lesion, being made easily short of breath after exercise, injection site bruising, rash, anxiety, appetite loss, hypokalaemia, fatigue aggravated, URI, itchiness, abdominal tenderness, depression, productive cough, upper abdominal pain, lung crackling, malaise, pneumonia and increased sweating. Common: heart murmur, stuffy nose, gingival bleeding, bruising over large areas of skin, lethargy, mouth swelling, hypotension, injection site itchiness, postprocedural haemorrhage, hives, loose stools, chest wall pain, dry skin, injection site granuloma/swelling, injection site changes in skin colour, mouth haemorrhage, skin nodule. Less common adverse effects include: lung scarring, tumour lysis syndrome, injection site cell death and sweet's syndrome.[7] Moderately emetogenic. Bleomycin (Blenemax, Bleo15k) N Other Inhibits DNA, RNA and protein synthesis Synthetic Peptide — too large to effectively show the structure here 1 December 2000 31 July 1973 IV, IM, SC Dermatologic (skin) reactions (occurs in around half of those receiving this drug) such as hives, rashes and changes in pigmentation of the skin, fever, swelling of the mouth and other mucous membranes, swelling of the spaces surrounding the air sacs, weight loss, high breathing rate, hair loss (1-10%), fatal lung reactions, anaphylaxis, finger/toe nail loss, itching, thickening of the skin & less commonly stroke, heart rate, hypotension, liver and kidney damage.[8] Minimal risk (<10%) for causing emesis (vomiting).[3] Minimally emetogenic. Bortezomib (Velcade) N Other Proteasome inhibitor Synthetic 14 February 2006 13 May 2003 IV, SC Common (>1%): nausea, vomiting, diarrhoea, constipation, abdominal pain, anorexia, dizziness, peripheral neuropathy, headache, musculoskeletal pain, thrombocytopaenia, neutropaenia, anaemia, fever, infection (including herpes virus reactivation), orthostatic hypotension (may require treatment), dehydration, cough, dyspnoea, rash and SC injection site reactions (e.g. redness). Rare (<1%): hypersensitivity reactions, raised liver enzymes, hepatitis, haemorrhage (e.g. GI, intracranial), heart failure, seizures, hearing loss, reversible posterior leucoencephalopathy syndrome (a neurological condition characterised by seizures and headaches), lung injury (can be permanent) and sweet's syndrome.[5] Busulfan (Tablet: Myleran. Injection: Busulfex) U (tab.), N (inj.) Alkylating agent See under alkylating agent Synthetic 24 August 1995 26 June 1954 PO, IV Common (>1%): myelosuppression. Low dose: skin hyperpigmentation. High dose: oral mucositis, oesophagitis, diarrhoea, constipation, CNS effects including seizures, tachycardia, alopecia, rash, hepatic sinusoidal obstruction syndrome, increased bilirubin and hepatic enzymes. Rare: dry skin and mucous membranes, skin reactions (including potentiation of skin reactions with radiotherapy) Low dose: Addison-like syndrome (weight loss, vomiting, diarrhoea, weight loss, weakness, fatigue, hypotension, hyperpigmentation), lung scarring, cataracts, gynaecomastia, jaundice and hepatitis. Carboplatin (Generics only) N Platinum compound Same as cisplatin Synthetic 9 November 1992 3 March 1989 IV Very common: myelosuppression, nausea, emesis, anaemia, magnesium loss, hair loss, muscle weakness, elevated ALP, central neutrotoxicity, elevated AST. Common: Immune hypersensitivity reaction and elevated bilirubin (leading, potentially, to yellow discolouration of the skin and eyes). Uncommon/rare: side effects include: Dehydration, mouth swelling, kidney damage and visual disturbances.[9][10] Moderately emetogenic. Chlorambucil (Leukeran) U Alkylating agent See under alkylating agent. Synthetic 23 November 2000 18 March 1957 PO Very common: myelosuppression. Unknown frequency: seizures, hallucinations, peripheral neuropathy, nausea, vomiting, lung scarring, GI effects, leukaemia, myelosuppression, hyperuricemia, infertility, hepatotoxicity & jaundice, type I hypersensitivity, rash, Stevens-Johnson syndrome (rare), toxic epidermal necrosis (rare), hives, erythema multiforme (rare), secondary malignancies.[11] Low emetogenic. Cisplatin (Generics only) N Platinum compound Produces apoptosis-inducing imperfections in the DNA of numerous cell varieties. Synthetic 13 August 1991 19 December 1978 IV Very common: nausea, vomiting (76-100%), nephrotoxocity (~30%), ototoxicity (especially in children; ~30% of those receiving the drug develop it), myelosuppression (~25-30%), anaphylaxis (1-20%) and alopecia. Highly emetogenic. Other side effects for which the frequency is unknown includes: seizures, brain damage (most often reversible), periphery neuropathy, diarrhoea, electrolyte abnormalities, hepatotoxicity and hyperuricaemia.[12] Cladribine (Leustatin, Litak, Movectro) N Antimetabolite Adenosine analogue Synthetic 12 February 1994 26 February 1993 IV, PO, SC Very common: fever (~70%; very common in those receiving this treatment for hairy cell leukaemia, but far less common in cases where the drug is being used for other purposes), fatigue (45%), nausea (28%), rash (27%), loss of appetite (17%) and vomiting (13%). Common: headache, dizziness, weakness, insomnia, trunk pain, infection, diarrhoea, constipation, abdominal pain, rash, pain and swelling at the injection site, oedema, tachycardia, cough, muscular aches, joint pain, malaise, myocardial ischaemia (when the heart muscle is deprived of oxygen), hypotension, anxiety, GI pain, flatulence, high heart rate, reversible and usually mild increases in bilirubin and AST, joint swelling, bone pain, secondary malignancies, haemorrhages, skin pain and hives. Uncommon/Rare: ataxia, drowsiness, lethargy, confusion, depression, weakness, seizure, numbness, swelling of the gallbladder and vein swelling.[5][13] Minimally emetogenic. Clofarabine (Evoltra) N Alkylating agent Adenosine analogue Synthetic 25 September 2009 28 December 2004 IV Very common: infection (~80%), vomiting, nausea, myelosuppression, diarrhoea, abdominal pain (~20-30%), weight loss, dermatitis (swelling of the skin), itchiness, fatigue, headache, fever, oedema, flushing, hypertension, hypotension, anxiety, pain, erythema, petechiae, chemotherapy-induced acral erythema, gingival haemorrhage, mucositis, oral candidiasis, cough, dyspnoea, pleural effusion, liver problems, haematuria, limb pain, myalgia, contusion and injection site pain. Common: back pain, bacteraemia, herpes simplex infections, sepsis, irritability, lethargy, somnolence, cellulitis and agitation. Infrequent: Stevens-Johnson syndrome, toxic epidermal necrolysis, pancreatitis, increased amylase and increased lipase. Moderately emetogenic. Cyclophosphamide (Cycloblastin, Endoxan) N Alkylating agent Mustard gas analogue. Causes chemical imperfections in the DNA that prevents its replication, which is vital to cell division Synthetic 20 January 1995 16 December 1959 IV, PO Very common: alopecia (40-60%), nausea, vomiting, GI toxicity, leucopenia, amenorrhoea and sterility (i.e. being infertile). Common: facial flushing, headache, rash, SIADH and nasal congestion (stuffy nose). Uncommon/rare: congestive heart failure (when the heart cannot pump enough blood to meet the demands of the body), Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), haemorrhagic cystitis, azoospermia, oligospermia, interstitial pneumonia, infectious disease and secondary malignancies (i.e. these people might get a new cancer on top of the cancer they already have).[14] Moderately-highly emetogenic (depends on the dose). Cytarabine (Generics only) N Antimetabolite Cytosine analogue Synthetic 24 October 2001 17 June 1969 IM, IT, IV, SC Common: weight loss, nausea, vomiting, diarrhoea, oral/anal swelling (i.e. swelling of the mouth and/or anus), vein swelling that results from blood clots, bleeding, myelosuppression, rash, fever and liver dysfunction. At a high dose: cerebral and cerebellar dysfunction (ataxia, drowsiness, coma), ocular toxicity (e.g. haemorrhagic conjunctivitis, keratitis), pulmonary toxicity (e.g. pneumonitis, pulmonary oedema, respiratory distress syndrome), severe GI ulceration. Infrequent/Rare include: Chemotherapy-induced acral erythema, headache, neuropathy (nerve disease; can affect the brain, spinal cord and/or the peripheral nerves), chest pain, pericarditis, pneumonia, kidney disease, infectious disease, sepsis, skin ulcers, skin ulcers, pericariditis, cellulitis (a bacterial infection of the skin), urinary retention (being unable to pass urine), neuritis (infection of the nerves), anaphylaxis and jaundice.[15] If given intrathecally it can lead to aseptic meningitis, that is, the swelling of the membranes that surround the brain without there being any obvious infectious cause.[5] Lowly-moderately emetogenic (depends on the dose). Dacarbazine (Generics only) N Alkylating agent Causes chemical imperfections in the DNA that prevent its replication, a vital step in the process of cell division Synthetic 19 June 2007 27 May 1975 IV Very common: nausea, vomiting, injection site pain, leucopenia and thrombocytopaenia. Highly emetogenic. Common: alopecia, rash, photosensitivity, weight loss, metallic taste and flu-like syndrome. Unknown frequency: Anaphylaxis, photosensitivity (i.e. being sensitive to light exposure, commonly this presents with skin rashes in exposed skin areas. Sunlight tends to be worse than artificial lighting for these sort of reactions), brain haemorrhage (i.e. a bleed into the brain), seizure, myelosuppression, hepatic necrosis (cell death in the liver; can lead to liver failure and death), hepatic (liver) vein thrombosis (blood clot; that is a blood clot in the vein that takes blood away from the liver) and hepatotoxicity.[16] Highly emetogenic. Daunorubicin (Generics only) N Anthracycline Inhibits topoisomerase II, among other actions leading to an inhibition of cell division and cell death. Bacterial species, Streptomyces peucetius 13 August 1991 19 December 1979 IV Very common: nausea, vomiting and arrhythmias. Unknown frequency: fever, cardiotoxicity (can be irreversible), flushing, swelling of the mouth, myelosuppression, hyperuricaemia (high levels of uric acid in the blood), red urine, alopecia, rash, darkening of previously irradiated (like during radiation therapy) areas, darkening of the skin under the fingernails and infertility. Moderately emetogenic. Doxorubicin (Adriamycin, Caelyx & generics) N Anthracycine Inhibits topoisomerase II, among other actions leading to an inhibition of cell division and cell death. Bacterial species, Streptomyces peucetius 8 April 1993 7 August 1973 IV Very common: myelosuppression, itchiness (~40%), fatigue (~30%), congestive heart failure (~30%) Vomiting (22%), rash (21%), alopecia (15%), weight loss (12%), constipation (12%) and diarrhoea (10%). Common: cardiomyopathy (chronic heart muscle disease). Unknown frequency: photosensitivity, cardiac dysrhythmias, necrotising colitis (basically where parts of the bowel [intestines] die), myelosuppression, hyperuricaemia, red urine and darkening of previous irradiated skin areas. Cardiotoxicity can be permanent with this drug. It is moderately emetogenic.[17] Moderately emetogenic. Etoposide (Etopophos, Vepesid & generics) U Podophyllotoxin Inhibits topoisomerase II. American Mayapple May 1991 10 November 1983 IV, PO Very common: leucopenia (>60%), nausea and vomiting (lowly-moderately emetogenic), thrombocytopaenia, alopecia (>20%), weight loss and diarrhoea. Common: pancytopaenia, swelling of the mouth, drops in blood pressure that occur when one stands up which can cause one to faint and peripheral neuropathy. Unknown frequency: malaise, shivering, muscle weakness, fever, swelling of the mucous membranes (such as in the throat, mouth, anus, etc.), hyperuricaemia and irritation near the injection site. Mildly emetogenic. Fludarabine (Fludara) N (inj.), A (tab.) Antimetabolite Adenosine analogue. Synthetic File:Fludarabine2DACS.svg 20 June 1995 18 April 1991 IV, PO Common: myelosuppression, fever, chills, infection, nausea, vomiting, diarrhoea, oral mucositis, constipation, malaise, numbness, visual and hearing disturbances, headache, insomnia, hyperglycaemia, oedema, maculopapular rash, itch, elevated liver enzymes. Infrequent: agitation, confusion, peripheral neuropathy, somnolence, GI bleeding, drug-induced pneumonitis (delayed effect occurring 3–28 days after repeated courses), autoimmune diseases (including thrombocytopaenia and haemolytic anaemia). Rare: severe neurotoxicity (with agitation, confusion, coma and seizures), haemorrhagic cystitis, Stevens-Johnson syndrome and toxic epidermal necrolysis.[5] Gemcitabine (Gemaccord, Gemplan, Gemzar & generics) N Antimetabolite Nucleoside analogue. Synthetic. 26 November 2008 15 May 1996 IV Very common: Nausea/Vomiting (70%), abnormality in liver function tests, pain, proteinuria, fever, haematuria, rash, myelosuppression, shortness of breath, constipation, diarrhoea, flu-like syndrome, haemorrhage, infection, alopecia, oedema and elevated bilirubin levels. Common: numbness, increased creatinine, injection site reactions, spasms of the muscles lining the air sacs (bronchospasms).[18] Rare: kidney failure, haemolytic uraemic syndrome, thrombotic thrombocytopenic purpura, skin reaction (including desquamation, vesiculation, ulceration), radiation recall, anaphylactoid reaction, capillary leak syndrome, heart attack, heart failure, arrhythmia, hypotension.[5] Mildly emetogenic.[5] Hydroxyurea (Hydrea) U Antimetabolite Inhibits the formation of DNA from RNA, hence inhibiting cell division. Synthetic December 1994 7 December 1967 PO Common (>1%): myelosuppression, haemolysis, oral mucositis, nausea, vomiting, weight loss, constipation, diarrhoea, maculopapular rash, facial erythema, itch and leg ulcers. Infrequent: hyperpigmentation, atrophy of skin and nails and cutaneous vasculitis. Rare: alopecia, skin cancer, radiation recall, dysuria, elevated serum creatinine, fever, chills, malaise, oedema, elevation of liver enzymes, dizziness, hallucinations, seizures and acute pulmonary reactions (diffuse pulmonary infiltrates or fibrosis, fever, dyspnoea).[5] Idarubicin (Zavedos) RA Anthracycline Inhibits topoisomerase II Semisynthetic 21 October 2010 27 September 1990 IV, PO Very common: Infection, nausea, vomiting, alopecia, haemorrhage, stomatitis, fever and abnormal liver function tests. Common: Hepatotoxicity, congestive heart failure, nephrotoxicity and myelosuppression. Less commonly: seizures, headache, periphery neuropathy, fever, chills, heart attack, chest pain, diarrhoea, red urine, etc.[19] Moderately emetogenic. Ifosfamide (Holoxan) N Alkylating agent Nitrogen mustard. Synthetic 30 October 2007 30 December 1988 IV Common (>1%): myelosuppression, weight loss, diarrhoea, constipation, alopecia, haemorrhagic cystitis, nephrotoxicity and neurotoxicity. Rare (<1%): cardiotoxicity (e.g. arrhythmias, heart failure; dose-related and generally reversible), thrombophlebitis and exacerbation of radiodermatitis. Neurotoxicity in this context refers to a condition that occurs in 10–40% of patients. Symptoms include somnolence, confusion, hallucinations, seizures, EPSE (movement disorders); may rarely result in coma. Symptoms generally resolve within 2–4 days if ifosfamide is stopped promptly.[5] Moderately emetogenic.[5] Mechlorethamine (not available in Aus) N Antimetabolite Mustard gas analogue that works by causing fatal flaws in the DNA of the person's cells hence preventing cell division Synthetic NA 15 March 1949 IV Severe nausea and vomiting occurs in >90% of patients. Unknown frequency side effects include: vertigo, chills, fever, tinnitus (ringing in the ears), thrombosis (blood clots), angiooedema, shortness of breath, haemolytic anaemia (anaemia due to the destruction of the red blood cells), hyperuricaemia, myelosuppression, jaundice, pain around the IV (needle) site, rash, dermatitis, erythema multiforme (a potentially fatal skin reaction), hives, impaired fertility, amenorrhoea, infrequent menstruation, azoospermia, oligospermia, allergic reactions, anaphylaxis and alopecia.[20] It is a highly emetogenic drug. Melphalan (Alkeran) N, U (2 mg tab.) Alkylating agent See under alkylating agent. Synthetic 4 September 2001 17 January 1964 IV, PO myelosuppression, diarrhoea, alopecia, allergic skin reactions and isolated limb perforation. Isolated limb perfusion is characterised by: myalgia and muscular atrophy (the wasting away of muscles). Infrequent: oral mucositis (common with high doses), lung scarring and pneumonitis, skin ulceration at IV injection site and skin cell death (rarely it can be severe enough to require new skin grafts). Mercaptopurine (Puri-Nethol) U Antimetabolite Inhibits ribonucleotide synthesis. Process is rather complex. The end result is that cancers resistant to thioguanine are likely resistant to mercaptopurine too. Synthetic ? (cannot seem to find this date) 11 September 1953 PO Very common: abnormal liver function tests. Common: nausea, vomiting, mouth swelling, thrombocytopaenia, hepatotoxicity, myelosuppression, rash, diarrhoea, dizziness, alopecia and leucopenia. Uncommon: Weight loss. Rare: fever, rash, joint pain, ulceration in the GI tract, alopecia, abnormally high level of pigmentation of the skin (i.e. ya skin will go dark) and secondary leukaemia.[5][21] Methotrexate (Methoblastin, methaccord) N (inj.); U, R (tab.) Antimetabolite Inhibits DHFR. Since methotrexate inhibits this enzyme it inhibits the synthesis of DNA which is a vital step in cell division. Synthetic 26 October 2000 7 December 1953 IM, IT, IV, PO, SC Very common: it can cause neurological (in this case pertaining to the brain and spinal cord) side effects in response to high dose treatment or intrathecal administration, reddening of the skin, hyperuricaemia, mouth ulcers, swelling of the gum and tongue, nausea, vomiting, diarrhoea, weight loss, a hole in the intestine that leads to the spilling of the contents of the intestines into the abdominal cavity (and possible an infection in the abdominal cavity) and bleeding into the intestines, swelling of the mucous membranes, leucopenia, thrombocytopaenia, kidney failure, azotemia (a high level of nitrogenous substances in the blood; these substances can cause toxicity), kidney disease and swelling of the throat. Common: alopecia, photosensitivity, rash, abdominal distress, malaise, fatigue, chills, fever, bleeding into the digestive tract, myelosuppression, interstitial lung disease, liver, cirrhosis and liver failure.[22] Mildly emetic, although at higher doses this side effect may become more severe. Mitozantrone (Onkotrone) N Anthracycline Inhibits DNA and RNA synthesis. Synthetic. 17 May 2000 23 December 1987 IV Very common: nausea, upper respiratory tract infection (e.g. cold or flu), urinary tract infection, constipation amenorrhoea, alopecia, diarrhoea, swollen mouth. Common: headache, back pain. Unknown frequency: myelosuppression, nail anomalies, raise liver enzymes and raised bilirubin and cardiotoxicity (tends to be less of a problem than with other anthracyclines).[23] Mildly emetogenic. Procarbazine (Natulan) N Alkylating agent See under alkylating agent. Synthetic. October 1995 22 July 1969 PO Common (>1%): myelosuppression, weight loss, drowsiness, depression, confusion, headache, sleep disturbances, dizziness, hallucinations, ataxia and peripheral neuropathy. Rare (<1%): diarrhoea, oral mucositis, alopecia, skin reactions (e.g. rash, itch, hyperpigmentation), pulmonary fibrosis, pneumonitis, haemolysis, hepatic dysfunction, fever, myalgia, arthralgia, nystagmus, diplopia, orthostatic hypotension and tachycardia.[5] Teniposide (Vurmon) N Podophyllotoxin Same as with etoposide. Semisynthetic 30 September 1991 14 July 1992 IV Common (>1%): myelosuppression, alopecia, nausea, vomiting, oral mucositis, diarrhoea, anorexia and hypersensitivity reactions. Rare (<1%): hypotension (with rapid infusion), peripheral neuropathy, rash, hives, inflammation or tissue death. Thioguanine (Lanvis) U Antimetabolite Guanine analogue. Synthetic ? (Can't seem to find this date) 18 January 1966 PO Very common: myelosuppression, hepatotoxicity. Common: nausea, vomiting, mouth swelling and diarrhoea. Infrequently: Rash and peripheral neuropathy. Rare: Intestinal cell death or, even, the formation of a hole in the intestine leading to the bacteria-rich intestinal content pouring into the abdominal cavity, potentially leading to an infection.[5] Mildly emetogenic. Vinblastine (Generics only) N Vinca alkaloid See under vinca alkaloids above. Rosy periwinkle plant. 21 June 1994 5 November 1965 IV Common (>1%): nausea, vomiting, oral mucositis, myelosuppression (major and dose-limiting), alopecia, vein irritation (e.g. injection site reactions and phlebitis [vein swelling]). Rare: Myocardial ischaemia, MI. Minimally emetogenic. Vincristine (Generics only) N Vinca alkaloid See under vinca alkaloids above. Rosy periwinkle plant. 7 October 1992 10 July 1963 IV Common (>1%): nausea, vomiting, oral mucositis, alopecia, vein irritation (e.g. injection site reactions and phlebitis [vein swelling]). Rare: Myocardial ischaemia, MI. Minimally emetogenic. Myelosuppression isn't usually a problem with vincristine. Minimally emetogenic. Vinflunine (Javlor) N Vinca alkaloid See under vinca alkaloids above. Rosy periwinkle plant. 11 February 2011 NA IV Common (>1%): nausea, myelosupression (major and dose limiting side effect), vomiting, oral mucositis, alopecia, vein irritation (e.g. injection site reactions and phlebitis [vein swelling]). Rare: Myocardial ischaemia, MI. Minimally emetogenic. Minimally emetogenic. Vinorelbine (Navelbine and generics) A Vinca alkaloid See under vinca alkaloids above. Rosy periwinkle plant. 31 May 2005 23 December 1994 PO, IV Common (>1%): nausea, vomiting, oral mucositis, myelosuppression (major and dose-limiting), alopecia, vein irritation (e.g. injection site reactions and phlebitis [vein swelling]). Rare: Myocardial ischaemia, MI. Minimally emetogenic. Non-cytotoxic neoplastics Monoclonal antibodies Alemtuzumab (Lemtrada, MabCampath, Remniq) N Antineoplastic antibody See under monoclonal antibodies Synthetic Protein, too large to show the structure here 10 May 2006 7 May 2001 IV Common (>1%): infusion-related reactions (hypotension, rigors, fever, shortness of breath, nausea, vomiting, chills, rashes and hives), lymphopenia (causes profound lymphopenia, which may be prolonged (full recovery may take >12 months). Risk of opportunistic infections is increased), neutropaenia, thrombocytopaenia, anaemia and infections. Infrequent: headache, anorexia, diarrhoea, increased sweating, pneumonitis, arrhythmias and pancytopaenia. Rare: hypersensitivity reactions, autoimmune haemolytic anaemia, autoimmune thrombocytopenia (when the bodies own defences attack the blood-clotting platelets) and progressive multifocal leucoencephalopathy (PML; an opportunistic infection due to the JC virus. This infection is nearly always fatal, regardless of treatment).[5] Minimally emetogenic.[5] Rituximab (Mabthera) N Antineoplastic antibody As above. Synthetic Protein, too large to show the structure here 6 October 1998 26 November 1997 IV Common (>1%): infusion-related reactions (fever, chills and/or rigors, nausea, vomiting, hives, itch, headache, bronchospasm, dyspnoea, angioedema, rhinitis, hypotension; most commonly occur after the first reaction), infection, neutropaenia (may be delayed-onset) and arrhythmias. Infrequent: thrombocytopaenia, anaemia, angina, MI and heart failure. Rare: haemolytic anaemia, aplastic anaemia (basically when the bone marrow becomes irreparably damaged causing pancytopaenia), serum sickness, severe skin conditions days to months after treatment (including Stevens-Johnson syndrome & toxic epidermal necrolysis), pulmonary infiltrates, pneumonitis, cranial neuropathy (vision or hearing loss), progressive multifocal leucoencephalopathy (PML). Minimally emetogenic.[5] Tyrosine kinase inhibitor Dasatinib (Spyrcel) N Tyrosine kianse inhibitor See under tyrosine kinase inhibitor Synthetic 15 January 2007 28 June 2006 PO Common: fluid retention, myelosuppression, haemorrhage (e.g. CNS, GI), nosebleeds, infections, diarrhoea, nausea, vomiting, anorexia, oral mucositis, fever, rash, headache, weakness, musculoskeletal pain, dyspnoea, pulmonary hypertension, chest pain, elevation of bilirubin or aminotransferases, hypocalcaemia, hypophosphataemia, hypokalaemia. Infrequently: cardiac dysfunction, heart failure, MI, arrhythmia, prolonged QT interval, kidney failure or hypersensitivity. Minimally emetogenic.[5] Imatinib (Glivec) N Tyrosine kinase inhibitor See under tyrosine kinase inhibitor Synthetic 13 August 2001 10 May 2001 PO Common: myelosuppression, nausea, vomiting, diarrhoea, anorexia, fluid retention (oedema, pleural effusion, pericardial effusion), muscle cramp, abnormal lab. values, arthralgia, skin reactions, hypophosphataemia, hypocalcaemia, GI bleeding, dyspnoea and headache. Infrequently: abnormalities in how the heart functions, heart failure, renal failure and gynaecomastia. Rare: oedema, anaphylaxis, GI perforation (may be fatal), hepatotoxicity, avascular necrosis, myopathy and rhabdomyolysis. Minimally emetogenic.[5] Nilotinib (Tasigna) A Tyrosine kinase inhibitor See under tyrosine kinase inhibitor Synthetic 17 January 2008 29 October 2007 PO Common: myelosuppression, electrolyte disturbances, hyperglycaemia, increased lipase or amylase, increased hepatic aminotransferases or bilirubin, rash, itch, nausea, vomiting, diarrhoea, constipation, headache, bone pain, arthralgia, muscle spasms and peripheral oedema. Infrequently: prolonged QT interval, peripheral arterial occlusive disease, pancreatitis, pleural effusion and pericardial effusion. Minimally emetogenic.[5] Miscellaneous other non-cytotoxic antineoplastics Arsenic trioxide (Phenasen) N Non-cytotoxic antineoplastic Not fully understood. Induces partial maturation of leukaemic cells and promotes apoptosis of leukaemic cells and may also inhibit angiogenesis. Synthetic As2O3 13 May 2009 25 September 2000 IV differentiation syndrome, similar to that with tretinoin, leucocytosis, neutropaenia, thrombocytopaenia, ventricular tachycardia, prolonged QT interval, torsades de pointes, complete atrioventricular block, nausea, vomiting, anorexia, diarrhoea, abdominal pain, oedema, arthralgia, myalgia, headache, peripheral neuropathy, hyperglycaemia, hypokalaemia, hypomagnesaemia, elevation of bilirubin or aminotransferases, hepatotoxicity, dermatitis, dry skin, itch and erythema.[5] Arsenic is known to be carcinogenic and hence secondary malignancies are possible. Moderately emetogenic.[5] Colaspase (Leunase) N Non-cytotoxic antineoplastic Works by catalysing the conversion of L-asparagine of asparagic acid, thus depleting a cancer cell's L-asparagine stores. Cancer cells synthesise their own asparagine whereas healthy cells can get it from other sources. Derived from a strain of E. Coli. Protein - too large to show here ? 18 November 2011 IM, IV Common: allergic reactions, nausea, vomiting, fatty changes in the liver, elevated aminotransferases and bilirubin, decreased albumin and calcium concentrations, haemorrhagic and thrombotic events, uraemia, pancreatitis and hyperglycaemia. Infrequently: transient proteinuria, CNS effects including depression or hyperexcitability; chills and fever (possibly caused by bacterial endotoxins in the product) and increased blood ammonia. Rare: transient myelosuppression, acute renal failure, diabetic ketoacidosis, parkinsonian-like syndrome, diarrhoea and oral mucositis. Minimally emetogenic.[5] Lenalidomide (Revlimid) N Non-cytotoxic antineoplastic Thalidomide analogue; mechanisms include direct cytotoxic effects on myeloma cells by induction of apoptosis, stimulation of T cell, interleukin-2 and interferon gamma production, inhibition of TNF alpha and interleukin-6 production, and reduced angiogenesis. Synthetic 20 December 2007 27 December 2005 PO Common (>1%): thromboembolic events (VTE, MI, stroke, TIA), neutropenia (dose-limiting), thrombocytopaenia (dose-limiting), anaemia, infection, constipation, diarrhoea, nausea, vomiting, anorexia, weight loss, taste disturbance, blurred vision, weakness, dizziness, headache, muscle cramps, tremor, dyspnoea, rash, itch, dry skin, hypotension, hypokalaemia, peripheral oedema, elevated liver enzymes and hypothyroidism. Rare (<1%): Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema, pneumonitis and hepatotoxicity. Secondary malignancies (mostly haematologic in nature) are possible. Minimally emetogenic.[5] Romidepsin (Isodax) N Histone deacetylase inhibitor Same as vorinostat. Synthetic 7 August 2013 5 November 2009 IV Very common: weakness, weight loss, constipation, diarrhoea, nausea, vomiting, anaemia, hypomagnesemia, neutropaenia, thrombocytopaenia and infections. Common: hypotension, ECG changes, exfoliative dermatitis, itchiness, hypocalcaemia, hypokalaemia, leucopenia, lymphopenia, laboratory abnormalities, hyperglycemia, hyponatremia and abnormal liver function test results.[24] Thalidomide (Thalomid) N Non-cytotoxic antineoplastic Mechanisms include direct cytotoxic effects on myeloma cells by induction of apoptosis, stimulation of T cell, interleukin-2 and interferon gamma production, inhibition of TNF alpha and interleukin-6 production, and reduced angiogenesis. Synthetic 22 December 2009 16 July 1998 PO Common: peripheral neuropathy, sedation, somnolence, headache, dizziness, agitation, vertigo, depression, thromboembolism, rash, constipation, nausea, vomiting, peripheral oedema, bradycardia, orthostatic hypotension, fainting, weight gain, leucopenia and hypothyroidism (mainly subclinical). Infrequently: thrombocytopaenia. Rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, pneumonitis, hepatotoxicity, hearing loss and amenorrhoea. Minimally emetogenic, when thalidomide was originally marketed in the 50s as a morning sickness pill it was being used to relieve nausea and vomiting so emesis isn't a big issue with it.[5] Tretinoin (also abbreviated ATRA; Vesanoid) N Non-cytotoxic antineoplastic Retinoic acid receptor activator; see main text for more info. Vitamin A analogue. 16 May 2007 22 November 1995 PO Common: differentiation syndrome, leucocytosis, headache, fever, dry skin and mucous membranes, rash, itch, elevated cholesterol and triglycerides, cardiac events including arrhythmia, oral mucositis, nausea, vomiting, abdominal pain, diarrhoea, constipation, pancreatitis, elevated liver enzymes, flushing, thrombosis, dizziness, confusion, intracranial hypertension and pseudotumour cerebri (mainly in children), anxiety, depression, numbness, insomnia, vision and hearing disorders and increased sweating. Rare: myositis (inflammation of the muscles), acute febrile neutrophilic dermatosis and genital ulceration. Minimally emetogenic.[5] Vorinostat (Zolinza) N Histone deacetylase inhibitor. Alters gene expression by inhibiting histones deacetylase. Synthetic 15 December 2009 6 October 2006 PO Very common: diarrhoea, fatigue, nausea, dysguesia, thrombocytopaenia, weight loss, muscle spasms, alopecia, chills, dry mouth, abnormal lab values, dizziness, constipation, vomiting, anaemia, peripheral oedema, headache, itchiness, cough, upper respiratory infection, loss of appetite and fever. Common: prolonged QT interval and pulmonary embolism (blood clot to the lungs). Secondary malignancies (mostly of the skin) can also occur.[25] Adjunctive antineoplastics Dexamethasone (Dexmethsone) N Corticosteroid Mimics the hormone, cortisol. Synthetic 26 May 1992 30 October 1958 PO, IM, IV Common: transient itching, burning or tingling in perineal area (after being delivered via IV) & typical corticosteroid effects which include: adrenal suppression, increased susceptibility to infection, masking of signs of infection, sodium and water retention, oedema, hypertension, hypokalaemia, hyperglycaemia, dyslipidaemia, osteoporosis, fractures, increased appetite, dyspepsia, delayed wound healing, skin atrophy, bruising, acne, facial flushing, hirsutism, growth retardation in children, myopathy, muscle weakness and wasting, fat redistribution (producing cushingoid appearance), weight gain, amenorrhoea, psychiatric effects and posterior subcapsular cataracts.[5] Infrequent: osteonecrosis, particularly of the femoral and humeral heads, ocular hypertension and glaucoma. Rare: peptic ulceration, hypersensitivity reactions, tendon rupture (especially of the Achilles tendon) and central serous chorioretinopathy.[5] Leucovorin (Generics only) N Antifolate antidote Converted by the body to THF, thus counteracting any toxic effects of methotrexate. Synthetic 13 August 1991 20 June 1952 IM, IV, PO Infrequent: allergic reactions, fever. Rare: seizure and fainting.[5] Prednisone (Lodotra, Panafcort, Sone) N Corticosteroid Mimics the hormone, cortisol. Synthetic 26 May 1997 21 February 1955 PO See above under typical corticosteroid effects.

Lymphomas

Hodgkin lymphoma

HL is usually very treatable with a 5-year survival rate of around 90%.^[26] Australians have a one in four-hundred and seventy-nine (1/479) chance of developing HL by the age of 85.^[27] Around 300 Australians are diagnosed with HL per year.^[27] I should probably explain the different staging of HL. Stage I HLs are limited to a single lymph node. Stage II HLs are limited to multiple lymph nodes on one side of the diaphragm (a sheet of muscle at the bottom of the lungs. Stage III HLs are limited to multiple lymph nodes on both sides of the diaphragm. Stage IV HLs have spread to extranodal (i.e. non-lymph node) organs as well as numerous lymph nodes. Stage I and Stage II HLs have a 5-year survival rate of 90%. Stage III HLs have a 5-year survival rate of 84%. Stage IV HLs have a 5-year survival rate of 65%. Notable sufferers of HL include Paul Allen, cofounder of Microsoft, and Richard Harris the actor that portrayed Albus Dumbledore in the first two Harry Potter films. The treatment for HL is mostly radiotherapy and chemotherapy.^[26]

The usual initial symptoms of HL include:

• A painless swollen lymph gland in your neck, groin or armpit
• Unexplained fevers
• Night sweats
• Weight loss
• Tiredness

Chemotherapeutic induction regimens (i.e. regimens designed to induce a remission; only one at a time is tried, however) for HL include: MOPP, ABVD, Stanford V and BEACOPP. MOPP stands for mechlorethamine, vincristine, procarbazine and prednisone. ABVD stands for adriamycin (this is a brand name used in the US; the generic name is doxorubicin), bleomycin, vinblastine and dacarbazine. Stanford V consists of doxorubicin, vinblastine, mustard (mustard gas analogues such as cyclophosphamide, mechlorethamine or ifosfamide), bleomycin, vincristine, etoposide and prednisone. BEACOPP stands for bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone.^[28]

Salvage chemotherapy (which is for cases where induction chemotherapy fails or if the patient experiences a reoccurance) in HL usually consists of (one of) the following chemotherapy regimens: ICE (ifosfamide, carboplatin and etoposide), DHAP (cisplatin, cytarabine and prednisone) or ESHAP (etoposide, methylprednisolone, cytarabine, cisplatin).^[28]

Non-Hodgkin lymphoma

NHL is usually rather treatable too and is more than 14 times more common than HL, although in kids both HL and NHL are roughly as common as each other.^[27] NHL makes up around 4% of cancer diagnoses in the US and accounts for around 4,300 cancer diagnoses in Australia each year.^[27] Overall Australian individuals have a one in forty-two (1/42) chance of developing NHL by the age of 85.^[27] Although it does heavily depend on the specific subtype as NHL consists of a whole set of different subtypes. Your odds of developing NHL increase as you get older and it most common affects those aged 65 years or older, although it can affect children and adolescents. The 5-year survival rate of NHL (taken as an average of all the different subtypes in the frequency at which they naturally occur) is around 71%. They have a number of different risk factors, including chronic inflammation (such as due to autoimmune conditions or unresolved infections), chromosomal abnormalities (Down's syndrome is probably the most notable chromosomal abnormality, although it's not one that's specifically associated with any NHL subtype), environmental factors (e.g. exposure to carcinogens like arsenic, fuel oil, tobacco smoke, etc.), immunodeficiency states (weak immune system caused by e.g. HIV infection), Epstein-Barr Virus (EBV; causative agent of Infectious Mononucleosis [Glandular Fever]) and Human T-cell lymphotropic virus [HTLV] infections. Subtypes of NHL include Burkitt's lymphoma (BL; I know of [although I didn't know them directly] someone that's died of this cancer. It's highly associated with EBV infections. More common in kids from central Africa or those with HIV infections), high-grade lymphoblastic lymphoma (HGLL), small noncleaved lymphoma (SNCL; the last two lymphomas are more common in kids), primary mediastinal diffuse large B-cell lymphoma (more common in females than males; this is the most common form of NHL), mantle cell lymphoma (MCL), anaplastic large cell lymphomas, mucosa-associated lymphoid tissue (MALT) lymphomas, follicular lymphomas (FL), small lymphocytic lymphoma (SLL), lymphoplasmacytoid lymphoma, T-cell lymphomas (TCL; specifically associated with the HTLV virus. This virus is spread via contact with an infected person's fluids, usually sexual contact. It is significantly more common in Japan than in other developed countries like Australia. It is also found in the Caribbean, Sub-Saharan African countries, South America and certain Iranian Jewish communities. HTLV is closely associated with the HIV virus), marginal zone lymphomas (MZL) and various others.^[29]

The usual initial symptoms of NHL include:^[27]

• Painless swelling of a lymph node in the neck, armpit or groin
• Unexplained and regular fevers
• Excessive sweating, especially at night
• Itchy skin
• Unintentional weight loss
• Tiredness
• Lethargy

NHL is usually treated with chemotherapy and radiotherapy (which is most frequently reserved for cases of indolent [non-aggressive] cancers that have not yet metastasised [spread]), although surgery may be attempted in select cases of non-metastatic lymphomas, especially gastrointestinal lymphomas such as MALT lymphoma.^[30] NHL chemotherapy regimens vary greatly according to the specific subtype if NHL and the degree of metastasis. Aggressive (fast-growing), yet non-metastatic NHL is usually treated with the chemotherapy regimen CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). CHOP is also used to treat metastatic indolent NHL. Metastatic aggressive NHL is usually treated with one of the following regimens: ^[30]

• CHOP
• ProMACE-CytaBOM (Prednisone, methotrexate , leucovorin, doxorubicin, cyclophosphamide, vincristine and etoposide)
• m-BACOD (Methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine and dexamethasone)
• MACOP-B (Methotrexate-leucovorin, doxorubicin, cyclophosphamide, vincristine, prednisone and bleomycin)
• Hyper-CVAD (cyclophosphamide, vincristine, doxorubicin, dexamethasone, alternating with methotrexate and cytarabine) plus rituximab
• Bendamustine and rituximab

Of these regimens CHOP is probably best tolerated in terms of side effects, but it also tends to be less effective than the others. TCLs tend to be more difficult to manage than other lymphomas with current drug treatments. TCLs (CTCLs) are usually treated with the following treatment regimens:^[30]

• CHOP + etoposide or gemcitabine
• Pralatrexate
• Alemtuzumab
• Denileukin diftitox
• Histone deacetylase (HDAC) inhibitors, that is substances that inhibit the enzyme histone deacetylase (HDAC), which deacetylates (which corresponds to the deactivation of) histones, proteins involved in gene expression, that is the generation of proteins like receptors or enzymes from the genetic code (DNA) of the cell. Consequently these drugs increase the expression of certain genes while reducing the expression of others. HDAC inhibitors used to treat CTCL include vorinostat and romidepsin. These drugs are mostly limited to cutaneous (i.e. it affects the skin) TCL. Valproate (comes in various forms, there's a sodium salt [sodium valproate], a semisodium salt, valproate semisodium and an acid form), the anticonvulsant (anti-seizure), anti-migraine and mood-stabilising drug is also a HDAC inhibitor being investigated as a potential chemotherapeutic agent.
• Lenalidomide
• Bortezomib

When highly aggressive NHLs like Burkitt's lymphoma are treated there's the potential for tumour lysis syndrome (TLS) to be seen, which is basically when a large number of cancer cells die in a short period of time leading the build up of their intracellular products (that is substances that were found inside the cancer cells before they were killed) in the extracellular fluid (the fluid outside cells). This overwhelms the body's natural mechanisms that are designed to keep the concentration of the different constituents of the extracellular fluid at a safe level and can lead to kidney failure, hyperkalaemia and hyperphosphataemia.^[31]

Leukaemias

Leukaemias and lymphomas are two of the most common childhood cancers. Although they are more common in the elderly than in children. The most common childhood cancer is actually acute lymphocytic leukaemia (ALL; accounts for around one-third of all childhood cancers),^[32] closely followed by acute myeloid leukaemia (AML).^[33] ALL has an fairly positive prognosis [outlook] with around 80% of kids with ALL achieving a cure and around 90% still alive at 5 years post-diagnosis.^[32] AML has a less positive prognosis, although it greatly depends on the subtype of the cancer. Overall the 5-year survival rate of paediatric AML is around 45-60%.^[33] In adults the prognosis tends to be less favourable, with ALL having a cure rate of around 25-40%.^[34] Stats on adult AML are more difficult to come by. Chronic leukaemias tend to be incurable, but their survival times tend to be favourable. I actually had a distant relative with chronic myeloid leukaemia (CML), whom I really learned died. Currently the median survival time for CML is over 5 years, with around 50-60% of patients still alive five years post-diagnosis.^[35] Most patients chronic lymphoblastic leukaemia (CLL) live for 5-10 years after their diagnosis.^[36] The 5-year survival rate of CLL in Australia is around 73%.^[37] Every year around 2,600 Australians (based on the 2009 stat of 2,576) are diagnosed with leukaemia, the most common leukaemia was CLL with ~1,100 diagnosed annually.^[37] After CLL comes AML at 900 diagnosed annually, ALL at 350 diagnosed annually and CML at 300 diagnosed annually.^[37] In 2007 around 1,211 people died of leukaemia with AML accounting for most of these deaths (721 in 2007).^[37] CLL came second in terms of deaths with 309 deaths in 2007 with CML at 92 deaths and ALL at 89 deaths.^[37]

The different leukaemias tend to present initially with the same constellation of symptoms, including:^[37]

• Tiredness
• Anaemia (pale complexion, weakness and breathlessness)
• Repeated infections
• Increased bruising and bleeding
• Bone pain
• Swollen, tender gums
• Skin rashes
• Headaches
• Vision problems
• Vomiting
• Enlarged lymph nodes
• Enlarged spleen which may cause abdominal discomfort
• Chest pains

The causes of leukaemia include exposure to radiation, carcinogens (e.g. benzene, tobacco smoke, alcohol [in excess] and arsenic) and HTLV infections. In most cases, however, no obvious cause can be found for the cancer. See many of these cancers occur in the elderly and it's just a danger of getting old. Acute leukaemias are usually treated with chemotherapy alone.^[37]

Acute lymphoblastic leukaemia

ALL is usually treated with chemotherapy. There are around five stages to treatment in ALL: induction (where the aim is to induce a remission), consolidation, interim maintenance (this stage is sometimes lumped in with maintenance), delayed intensification, and maintenance. The usual induction regimen in adults and children includes: vincristine, prednisone, an anthracycline (e.g. doxorubicin or daunorubicin) and cyclophosphamide and/or asparaginase.^[38][39] After this comes the consolidation phase which is designed to get rid of any leukaemia cells hiding in the brain or testis and hence prevent any relapse.^[38][39] The consolidation phase regimen usually consists of: cytarabine, cyclophosphamide and/or anthracycline (adult cases) and/or mercaptopurine.^[38][39] After this comes interim maintenance which is when we're trying to keep back the cancer and prevent relapses while simultaneously giving the bone marrow the chance to recover from the damage done by the previous two stages of treatment.^[38][39] The usual interim maintenance regimen consists of vincristine and intravenous methotrexate.^[38][39] This treatment is continued for 4-8 weeks, after this comes the delayed intensification stage, information on which is not easy to obtain but I would guess that it would consist of the regimen used for induction.^[38][39] It's designed to kill any remaining resistant leukaemia cells.^[38][39] This stage appears to be mostly for children with ALL as I can't find any information regarding this stage in adults.^[38][39] After this comes maintenance which can go on for indefinite period of time. Information on what's involved in this stage for adults is hard to come by but for kids it consists of three-monthly intrathecal, monthly vincristine treatments, steroid treatments, daily 6-MP and weekly MTX.^[38][39] Sometimes radiotherapy of the head might be tried if it spreads there (sometimes it likes to hide out [away from the drugs that can't usually penetrate the BBB] in the brain and spinal cord).^[39] It may also be used to completely destroy the bone marrow so that a bone marrow transplant can be performed.^[38]

Acute myeloid leukaemia

AML is usually treated with chemotherapy alone.^[40] Chemotherapy regimens used to treat AML include: "3 and 7" which consists 3 days of a 15-30 minute infusion of an anthracycline like doxorubicin, daunorubicin or idarubicin or an anthracenedione (mitoxantrone; works by inhibiting topoisomerase II) and 7 days of 24-hr daily infusions of cytarabine.^[40] This sort of regimen achieves remissions in around 50% of patients with a single course and a further 10-15% achieve a remission with a second course of this regimen.^[40]

Acute promyelocytic leukaemia

One subtype of AML, acute promyelocytic leukaemia (APL) has been reported to possess a 12-year disease-free survival rate of an estimated 69%.^[41] This is particularly impressive because of the fact that the median age at diagnosis is 40, and the older the patient the worse the prognosis as a general rule of thumb (although other factors do come into the question, of course). APL is usually treated with anthracyclines, tretinoin and even a form of arsenic, arsenic trioxide. APL is the only malignancy (cancer) that tretinoin and arsenic trioxide is used to treat. Tretinoin is actually a form of vitamin A.

Chronic lymphocytic leukaemia

CLL is a form of leukaemia that predominantly affects the elderly (median age is about 72 years). It is more common in those of European ancestry (i.e. whites) than blacks (in this context as I'm reading this from an American source refers mostly to Africans). It is fairly uncommon in Asians, although it is possible this could be due to under-diagnosis in Asian countries. It is also more common in men than in women (men-to-women ratio of 1.7:1).^[36] Some cases have a genetic component, in these cases the median age is less at 58 years.^[36]

CLL is not usually considered curable, but because it is a slow-growing cancer, periods (most often months) of disease-free survival are usually possible with treatment and palliative care.^[42] The only known cure is allogeneic stem cell transplantation (stem cell transplant from a genetically related donor), but this is not usually an option in the elderly, which are those that most commonly develop CLL.^[42] Other treatments are surgery (spleen removal as it may harbour cancer cells sometimestimes), radiation and chemotherapy.^[42]

Drug treatments for CLL include: chlorambucil, fludarabine, alemtuzumab and rituximab. There are a few monoclonal antibodies available in the US for this disease that aren't available in Australia. One such drug, obinutuzumab has been the subject of a recent clinical trial. In this trial obinutuzumab combined with chlorambucil (henceforth to be called OCH combo) produced superior responses to rituximab plus chlorambucil (RCH combo). Median progression-free survival times were 27 months for those on the OCH combo compared to just 15 months with RCH. Overall response rates were also higher (78% vs. 65%) for the OCH-treated patients. The number of patients for which no cancer could be detected in the blood was also higher in the patients treated with OCH (37.7% vs. 3.3%). Likewise those for whom bone marrow biopsies failed to detect any cancer was also higher in those treated with OCH (19.5% vs. 2.6%).^[43]

Hairy cell leukaemia

Hairy cell leukaemia (HCL) is a subtype of CLL that's limited to the B cells. The median age of patients at diagnosis is about 52 years. Male-to-female ratio is about 4-5:1. As with CLL it is less common in those of Asian and African ancestry. It tends to be more responsive to treatment than CLL in general. It is usually initially treated with an IV/SC injection of cladribine for 7 days (either a continuous infusion with cladribine or 2 hour IV/SC daily injections at a higher dose for 5 days).^[44] If it relapses after this treatment regimen rituximab or interferon alfa 2b may be used.^[44][45]

Chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) tends to be incurable without a bone marrow transplant (where they destroy the old marrow with radiation and drugs and take bone marrow from a close relative and give it to you) or stem cell transplant. Despite this chemotherapy does tend to prolong survival. As may surgery (namely the removal of the spleen). Current TGA-approved cytotoxic treatments include: busulfan and hydroxyurea. Other TGA-approved non-cytotoxic treatments include the tyrosine kinase inhibitors: dasatinib, imatinib and nilotinib and the cytokine product peginterferon alfa 2a.^[46] In the US there are 3 additional drugs that are approved for the clinical treatment of CML, and they include the two tyrosine kianse inhibitors: bosutinib and ponatinib (which may possess the edge in certain cases of treatment-resistance). The other drug is a natural product, omacetaxine, which is a semisynthetic derivative of a compound derived from cephalotaxus harringtonii, a plant native to Japan and China. It works via a completely different mechanism to all other antineoplastics listed here and hence may be particularly effective in treatment-resistant cases of CML.^[47]

Multiple myeloma

Multiple myeloma or MM for short is a cancer that arises from the plasma cells of the blood. These are the cells that produce antibodies and are mature B cells. It begins in the bone marrow and often the bone in which the bone marrow is found becomes severely damaged by the MM leading to an increased risk of bone fractures. It accounts for about 10% of all blood cancers. The 5-year survival rate is about 35%, and is more favourable in younger patients compared to their elderly counterparts. It is more common in Africans than Europeans. It is about half as common in Asians as opposed to Europeans. It is 1.4x more common in men than in women.^[48] It is generally considered incurable.^[48] TGA-approved cytotoxic antineoplastics used to treat MM include: cyclophosphamide, melphalan, doxorubicin, vincristine and bortezomib. Corticosteroids like prednisone and dexamethasone are often incoorporated into chemotherapy regimens for MM. Cytokine products used to treat MM include interferon alfa-2a and interferon alfa-2b. On top of this the two non-cytotoxic agents: thalidomide and lenalidomide.^[49] Additionally bone marrow and stem cell transplants can be used to treat MM.^[49] Radiotherapy of severely affected bones is sometimes attempted too.^[49]

Notes

Reference List