Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled In popular usage, it usually refers to antineoplastic drugs used to treat cancer or the combination of these drugs into a standardized treatment regimen. Antineoplastics (or "antitumor antibiotics" or "noncovalent DNA-binding drugs" or " Cytotoxic antibiotics" see also Neoplastics are Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Chemotherapy regimens are often identified with acronyms identifying the agents used in combination

In its non-oncological use, the term may also refer to antibiotics (antibacterial chemotherapy). Oncology is the branch of medicine that studies Tumors ( Cancer) and seeks to understand their development diagnosis treatment and prevention In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa In that sense, the first modern chemotherapeutic agent was Paul Ehrlich's arsphenamine, an arsenic compound discovered in 1909 and used to treat syphilis. Paul Ehrlich ( March 14, 1854 &ndash August 20, 1915) was a German Scientist who won the 1908 Nobel Arsphenamine, also known as Salvarsan and 606, is a drug that was used to treat Syphilis and trypanosomiasis. Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. This was later followed by sulfonamides discovered by Domagk and penicillin discovered by Alexander Fleming. There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide Gerhard Johannes Paul Domagk ( October 30, 1895 &ndash April 24, 1964) was a German Pathologist and Bacteriologist Penicillin (sometimes abbreviated PCN or pen) is a group of Beta-lactam antibiotics used in the treatment of Bacterial Infections Sir Alexander Fleming (6 August 1881 &ndash 11 March 1955 was a Scottish Biologist and Pharmacologist.

Other uses of cytostatic chemotherapy agents (including the ones mentioned below) are the treatment of autoimmune diseases such as multiple sclerosis and rheumatoid arthritis and the suppression of transplant rejections (see immunosuppression and DMARDs). Autoimmune diseases arise from an overactive Immune response of the body against substances and tissues normally present in the body Multiple sclerosis (abbreviated MS also known as disseminated sclerosis or encephalomyelitis disseminata) is an autoimmune condition in which the Rheumatoid arthritis ( RA) is a chronic systemic autoimmune disorder that causes the Immune system to attack the Joints, where Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient Immunosuppression involves an act that reduces the activation or Efficacy of the Immune system. Disease-modifying antirheumatic drugs ( DMARDs) is a category of drugs used in many autoimmune disorders to slow down disease progression

Contents 1 History 2 Principles 3 Treatment schemes 4 Types 4.1 Alkylating agents (L01A) 4.2 Anti-metabolites (L01B) 4.3 Plant alkaloids and terpenoids (L01C) 4.3.1 Vinca alkaloids (L01CA) 4.3.2 Podophyllotoxin (L01CB) 4.3.3 Taxanes (L01CD) 4.4 Topoisomerase inhibitors (L01CB and L01XX) 4.5 Antitumour antibiotics (L01D) 4.6 Monoclonal antibodies 4.7 Hormonal therapy 5 Dosage 6 Delivery 7 Newer and experimental approaches 7.1 Hematopoietic stem cell transplant approaches 7.2 Isolated infusion approaches 7.3 Targeted delivery mechanisms 7.4 Nanoparticles 8 Side-effects 8.1 Immunosuppression and myelosuppression 8.2 Nausea and vomiting 8.3 Other side effects 9 See also 10 References 11 External links

History

Further information: History of cancer chemotherapy

The use of chemical substances and drugs as medication dates back to the ancient Indian system of medicine called Ayurveda which uses many metals besides herbs for treatment of a large number of ailments. The era of cancer Chemotherapy began in the 1940s with the first use of Nitrogen mustards and Folic acid antagonist drugs A chemical substance is a Material with a definite chemical composition. Medication, also referred to as medicine, can be loosely defined as any substance intended for use in the diagnosis cure mitigation treatment or prevention of disease India, officially the Republic of India (भारत गणराज्य inc-Latn Bhārat Gaṇarājya; see also other Indian languages) is a country Ayurveda ( Devanāgarī: आयुर्वॆद the 'science of life' is a system of Traditional medicine native to India, and practiced in other More recently, Persian physician, Muhammad ibn Zakarīya Rāzi (Rhazes), in the 10th century, introduced the use of chemicals such as vitriol, copper, mercuric and arsenic salts, sal ammoniac, gold scoria, chalk, clay, coral, pearl, tar, bitumen and alcohol for medical purposes. Sulfuric (or sulphuric acid, H 2 S[[oxygen O]]4 is a strong Mineral acid. Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Mercury (ˈmɜrkjʊri also called quicksilver or hydrargyrum, is a Chemical element with the symbol Hg ( Latinized hydrargyrum Arsenic (ˈɑrsənɪk is a Chemical element that has the symbol As and Atomic number of 33 Salt is a Dietary mineral composed primarily of Sodium chloride that is essential for Animal life but toxic to most land plants Sal ammoniac is a rare mineral composed of Ammonium chloride, NH4Cl Gold (ˈɡoʊld is a Chemical element with the symbol Au (from its Latin name aurum) and Atomic number 79 Scoria is a textural term for macrovesicular Volcanic rock. It is commonly but not exclusively Basaltic or andesitic in composition Chalk (ʧɔːk is a soft white porous Sedimentary rock, a form of Limestone composed of the Mineral Calcite. Clay is a naturally occurring material composed primarily of fine-grained Minerals which show plasticity through a variable range of Water content, and Corals are Marine organisms from the class Anthozoa and exist as small Sea anemone –like Polyps typically in colonies of many A pearl is a hard roundish object produced within the soft tissue (specifically the mantle) of a living shelled Mollusk. Tar is a viscous black Liquid derived from the Destructive distillation of organic matter Bitumen is a mixture of organic Liquids that are highly Viscous, black sticky entirely soluble in Carbon disulfide, and composed primarily In Chemistry, an alcohol is any Organic compound in which a Hydroxyl group ( - O[[hydrogen H]]) is bound to a Carbon ^[1]

The first drug used for cancer chemotherapy, however, dates back to the early 20th century, though it was not originally intended for that purpose. Mustard gas was used as a chemical warfare agent during World War I and was studied further during World War II. The sulfur mustards, of which mustard gas ( Bis (2-chloroethyl sulfide is a member are a class of related Cytotoxic, Vesicant Chemical Chemical warfare involves using the toxic properties of Chemical substances to kill injure or incapacitate an enemy. World War I (abbreviated WWI; also known as the First World War, the Great War, and the War to End All World War II, or the Second World War, (often abbreviated WWII) was a global military conflict which involved a majority of the world's nations, including During a military operation in World War II, a group of people were accidentally exposed to mustard gas and were later found to have very low white blood cell counts^[2]. It was reasoned that an agent that damaged the rapidly growing white blood cells might have a similar effect on cancer. Therefore, in the 1940s, several patients with advanced lymphomas (cancers of certain white blood cells) were given the drug by vein, rather than by breathing the irritating gas. Their improvement, although temporary, was remarkable. ^{[3] [4]} That experience led researchers to look for other substances that might have similar effects against cancer. As a result, many other drugs have been developed to treat cancer, and drug development since then has exploded into a multi-billion dollar industry. The targeted-therapy revolution has arrived, but the principles and limitations of chemotherapy discovered by the early researchers still apply. ^[5]

Principles

Cancer is the uncontrolled growth of cells coupled with malignant behavior: invasion and metastasis. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled The cell is the structural and functional unit of all known living Organisms It is the smallest unit of an organism that is classified as living and is often called Malignant (from the Latin roots mal- = "bad" and -genus = "born" is a medical term used to describe a severe and progressively worsening disease Metastasis ( Greek: displacement μετά=next + στάσις=placement, plural metastases) sometimes abbreviated mets, Cancer is thought to be caused by the interaction between genetic susceptibility and environmental toxins.

Broadly, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. As these drugs cause damage to cells they are termed cytotoxic. Some drugs cause cells to undergo apoptosis (so-called "programmed cell death").

Unfortunately, scientists have yet to identify specific features of malignant and immune cells that would make them uniquely targetable (barring some recent examples, such as the Philadelphia chromosome as targeted by imatinib). Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with Chronic myelogenous leukemia (CML Imatinib is a drug used to treat certain types of Cancer. It is currently marketed by Novartis as Gleevec ( USA) or Glivec This means that other fast dividing cells such as those responsible for hair growth and for replacement of the intestinal epithelium (lining) are also often affected. Hair is a keratinised protein filament that grows through the epidermis from follicles deep within the Dermis. In Anatomy, the intestine is the segment of the alimentary canal extending from the Stomach to the Anus and in humans and other mammals consists In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body However, some drugs have a better side-effect profile than others, enabling doctors to adjust treatment regimens to the advantage of patients in certain situations. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery. A physician, medical practitioner or medical doctor who practices Medicine, and is concerned with maintaining or restoring human Health

As chemotherapy affects cell division, tumors with high growth fractions (such as acute myelogenous leukemia and the aggressive lymphomas, including Hodgkin's disease) are more sensitive to chemotherapy, as a larger proportion of the targeted cells are undergoing cell division at any time. Acute myeloid leukemia ( AML) also known as acute myelogenous leukemia, is a Cancer of the Myeloid line of White blood cells characterized Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) Hodgkin's lymphoma, also known as Hodgkin's disease is a type of Lymphoma first described by Thomas Hodgkin in 1832 Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly.

Drugs affect "younger" tumors (i. e. more differentiated) more effectively, because mechanisms regulating cell growth are usually still preserved. With succeeding generations of tumor cells, differentiation is typically lost, growth becomes less regulated, and tumors become less responsive to most chemotherapeutic agents. Near the center of some solid tumors, cell division has effectively ceased, making them insensitive to chemotherapy. Another problem with solid tumors is the fact that the chemotherapeutic agent often does not reach the core of the tumor. Solutions to this problem include radiation therapy (both brachytherapy and teletherapy) and surgery. Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Brachytherapy (from the Greek brachy, meaning "short" also known as sealed source radiotherapy or endocurietherapy, is a form of External beam radiotherapy otherwise known as teletherapy, is the most frequently used form of Radiotherapy. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental

Over time, cancer cells become more resistant to chemotherapy treatments. Recently, scientists have identified small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Research on p-glycoprotein and other such chemotherapy efflux pumps, is currently ongoing. P-glycoprotein (abbreviated as P-gp or Pgp) is a well-characterized Human ABC-transporter of the MDR / TAP subfamily Medications to inhibit the function of p-glycoprotein are undergoing testing as of June, 2007 to enhance the efficacy of chemotherapy. P-glycoprotein (abbreviated as P-gp or Pgp) is a well-characterized Human ABC-transporter of the MDR / TAP subfamily

Treatment schemes

There are a number of strategies in the administration of chemotherapeutic drugs used today. Chemotherapy may be given with a curative intent or it may aim to prolong life or to palliate symptoms.

Combined modality chemotherapy is the use of drugs with other cancer treatments, such as radiation therapy or surgery. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled Radiation therapy (or radiotherapy) is the medical use of Ionizing radiation as part of Cancer treatment to control Malignant Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental Most cancers are now treated in this way. Combination chemotherapy is a similar practice which involves treating a patient with a number of different drugs simultaneously. The drugs differ in their mechanism and side effects. The biggest advantage is minimising the chances of resistance developing to any one agent.

In neoadjuvant chemotherapy (preoperative treatment) initial chemotherapy is aimed for shrinking the primary tumour, thereby rendering local therapy (surgery or radiotherapy) less destructive or more effective. Neoadjuvant chemotherapy refers to Drug treatment given to people with Cancer prior to surgery

Adjuvant chemotherapy (postoperative treatment) can be used when there is little evidence of cancer present, but there is risk of recurrence. Adjuvant chemotherapy is a term used to describe the role of Chemotherapy relative to other cancer treatments This can help reduce chances of resistance developing if the tumour does develop. It is also useful in killing any cancerous cells which have spread to other parts of the body. This is often effective as the newly growing tumours are fast-dividing, and therefore very susceptible.

Palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, a better toxicity profile is generally expected.

All chemotherapy regimens require that the patient be capable of undergoing the treatment. Performance status is often used as a measure to determine whether a patient can receive chemotherapy, or whether dose reduction is required. In Medicine ( Oncology and other fields performance status is an attempt to quantify Cancer patients' general wellbeing

Types

The majority of chemotherapeutic drugs can be divided in to alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. An alkylating antineoplastic agent is an Alkylating agent that attaches an alkyl group to DNA. An antimetabolite is a chemical with a similar structure to a substance (a Metabolite) required for normal biochemical reactions yet different enough to interfere with the normal Anthracyclines (or anthracycline antibiotics) are a class of drugs used in cancer chemotherapy. This article is about the chemical compounds alkaloids For the Pharmaceutical company in the Republic of Macedonia see Alkaloid (company. Topoisomerases (type I, type II) are Isomerase Enzymes that act on the topology of DNA. All of these drugs affect cell division or DNA synthesis and function in some way. Cell division is a process by which a cell, called the parent cell divides into two or more cells called daughter cells. Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known

Some newer agents don't directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e. Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell A tyrosine kinase is an Enzyme that can transfer a Phosphate group from ATP to a Tyrosine residue in a Protein. g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors). Imatinib is a drug used to treat certain types of Cancer. It is currently marketed by Novartis as Gleevec ( USA) or Glivec Chronic myelogenous (or myeloid leukemia ( CML) is a form of Leukemia characterized by the increased and unregulated growth of predominantly Myeloid cells A gastrointestinal stromal tumor ( GIST) is a rare Tumor of the Gastrointestinal tract (1-3% of all gastrointestinal malignancies

In addition, some drugs may be used which modulate tumor cell behaviour without directly attacking those cells. Hormone treatments fall into this category of adjuvant therapies.

Where available, Anatomical Therapeutic Chemical Classification System codes are provided for the major categories. The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug

Alkylating agents (L01A)

Main article: Alkylating antineoplastic agent

Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. An alkylating antineoplastic agent is an Alkylating agent that attaches an alkyl group to DNA. " Electronegativity " is the opposite of " Electropositivity," which describes an element's ability to donate electrons Cisplatin and carboplatin, as well as oxaliplatin are alkylating agents. Cisplatin, cisplatinum or cis -diamminedichloridoplatinum(II (CDDP is a Platinum -based Chemotherapy drug used to treat CARBOplatin is a Chemotherapy drug used against some forms of Cancer (mainly ovarian carcinoma lung head and neck cancers Oxaliplatin is a Platinum -based Chemotherapy drug in the same family as Cisplatin and Carboplatin.

Other agents are mechlorethamine, cyclophosphamide, chlorambucil. Mechlorethamine also known as chlormethine, mustine, nitrogen mustard and HN2 and sold under the brand name Mustargen, is the prototype Cyclophosphamide (the generic name for Cytoxan Neosar Revimmune also known as cytophosphane is a Nitrogen mustard alkylating agent, from the oxazophorines group Chlorambucil (marketed as Leukeran by GlaxoSmithKline) is a Chemotherapy drug that has been mainly used in the treatment of Chronic lymphocytic They work by chemically modifying a cell's DNA.

Anti-metabolites (L01B)

Main article: antimetabolite

Anti-metabolites masquerade as purine ((azathioprine, mercaptopurine)) or pyrimidine - which become the building blocks of DNA. An antimetabolite is a chemical with a similar structure to a substance (a Metabolite) required for normal biochemical reactions yet different enough to interfere with the normal An antimetabolite is a chemical with a similar structure to a substance (a Metabolite) required for normal biochemical reactions yet different enough to interfere with the normal Purine ( 1) is a heterocyclic Aromatic Organic compound, consisting of a Pyrimidine ring fused to an Imidazole ring Mercaptopurine (also called 6-Mercaptopurine 6-MP or its brand name Purinethol) is an Immunosuppressive drug used to treat Leukemia. Pyrimidine is a Heterocyclic Aromatic Organic compound similar to Benzene and Pyridine, containing two Nitrogen Atoms They prevent these substances becoming incorporated in to DNA during the "S" phase (of the cell cycle), stopping normal development and division. The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication They also affect RNA synthesis. Due to their efficiency, these drugs are the most widely used cytostatics.

Plant alkaloids and terpenoids (L01C)

These alkaloids are derived from plants and block cell division by preventing microtubule function. This article is about the chemical compounds alkaloids For the Pharmaceutical company in the Republic of Macedonia see Alkaloid (company. Plants are living Organisms belonging to the kingdom Plantae. Microtubules are one of the components of the Cytoskeleton. They have a diameter of 25 nm and length varying from 200 nanometers to 25 micrometers Microtubules are vital for cell division and without them it can not occur. The main examples are vinca alkaloids and taxanes. Catharanthus ( Madagascar Periwinkle) is a genus of eight species of Herbaceous Perennial plants seven endemic to the island of The taxanes are Diterpenes produced by the plants of the genus Taxus (yews

Vinca alkaloids (L01CA)

Vinca alkaloids bind to specific sites on tubulin, inhibiting the assembly of tubulin into microtubules (M phase of the cell cycle). Mitosis is the process in which a Eukaryotic cell separates the Chromosomes in its Cell nucleus, into two identical sets in two daughter nuclei The cell cycle, or cell-division cycle, is the series of events that take place in a eukaryotic cell leading to its replication They are derived from the Madagascar periwinkle, Catharanthus roseus (formerly known as Vinca rosea). Catharanthus ( Madagascar Periwinkle) is a genus of eight species of Herbaceous Perennial plants seven endemic to the island of The vinca alkaloids include:

• Vincristine
• Vinblastine
• Vinorelbine
• Vindesine

Podophyllotoxin (L01CB)

Podophyllotoxin is a plant-derived compound used to produce two other cytostatic drugs, etoposide and teniposide. Vincristine (brand name Oncovin also known as leurocristine, is a vinca Alkaloid from the Madagascar periwinkle ( Catharanthus roseus, Vinblastine is an anti-mitotic drug used to treat certain kinds of Cancer, including Hodgkin's lymphoma, non-small cell Lung cancer Vinorelbine (Navelbine is an anti-mitotic Chemotherapy drug that is given as a treatment for some types of cancer including Breast cancer and non-small Vindesine is an anti-mitotic Vinca alkaloid used in Chemotherapy. Podophyllotoxin, otherwise known as podofilox, is a non- Alkaloid Toxin in the Lignan family present at concentrations of 0 Etoposide phosphate (brand names Eposin, Etopophos, Vepesid, VP-16) is an inhibitor of the Enzyme Topoisomerase II. Teniposide ( Vumon, VM-26) is a chemotherapeutic Medication mainly used in the treatment of childhood Acute lymphocytic leukemia. They prevent the cell from entering the G1 phase (the start of DNA replication) and the replication of DNA (the S phase). The G1 phase is a period in the Cell cycle during Interphase, after Cytokinesis and before the S phase. The S phase, short for synthesis phase, is a period in the Cell cycle during Interphase, between G1 phase and the G2 phase. The exact mechanism of its action still has to be elucidated.

The substance has been primarily obtained from the American Mayapple (Podophyllum peltatum). Podophyllum peltatum (the mayapple is a Herbaceous Perennial plant in the family Berberidaceae, native to the eastern part of North Recently it has been discovered that a rare Himalayan Mayapple (Podophyllum hexandrum) contains it in a much greater quantity, but as the plant is endangered, its supply is limited. The perennial herb Podophyllum hexandrum (syn P emodi) bearing the common names Himalayan mayapple or Indian may apple, is native to Studies have been conducted to isolate the genes involved in the substance's production, so that it could be obtained recombinantively. Genetic engineering, Recombinant DNA technology, genetic modification/manipulation (GM and gene splicing are terms that apply to the direct

Taxanes (L01CD)

The prototype taxane is the natural product paclitaxel, originally known as Taxol and first derived from the bark of the Pacific Yew tree. A natural product is a Chemical compound or substance produced by a living organism - found in nature that usually has a pharmacological or biological activity for use in pharmaceutical Paclitaxel is a Mitotic inhibitor used in Cancer Chemotherapy. Paclitaxel is a Mitotic inhibitor used in Cancer Chemotherapy. Taxus brevifolia ( Pacific Yew or Western Yew) is a conifer native to the Pacific Northwest of North America. Docetaxel is a semi-synthetic analogue of paclitaxel. Docetaxel is a clinically well established anti-mitotic Chemotherapy Taxanes enhance stability of microtubules, preventing the separation of chromosomes during anaphase. A chromosome is an organized structure of DNA and Protein that is found in cells. Anaphase, from the Ancient Greek ἀνά (up and φάσις (stage is the stage of Mitosis when Chromosomes

Topoisomerase inhibitors (L01CB and L01XX)

Topoisomerases are essential enzymes that maintain the topology of DNA. Topoisomerases (type I, type II) are Isomerase Enzymes that act on the topology of DNA. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Topology ( Greek topos, "place" and logos, "study" is the branch of Mathematics that studies the properties of Inhibition of type I or type II topoisomerases interferes with both transcription and replication of DNA by upsetting proper DNA supercoiling. Transcription is the synthesis of RNA under the direction of DNA DNA replication is the process of copying a double-stranded DNA molecule to form two double-stranded molecules In a "relaxed" double-helical segment of DNA, the two strands twist around the helical axis once every 10

• Some type I topoisomerase inhibitors include camptothecins: irinotecan and topotecan. Irinotecan is a chemotherapy agent that is a topoisomerase 1 inhibitor. Topotecan hydrochloride (trade name Hycamtin) is a chemotherapy agent that is a topoisomerase 1 inhibitor.

• Examples of type II inhibitors include amsacrine, etoposide, etoposide phosphate, and teniposide. Amsacrine is an Antineoplastic agent Its planar fused ring system can intercalate into the DNA of Tumor cells thereby altering the major and Etoposide phosphate (brand names Eposin, Etopophos, Vepesid, VP-16) is an inhibitor of the Enzyme Topoisomerase II. Etoposide phosphate (brand names Eposin, Etopophos, Vepesid, VP-16) is an inhibitor of the Enzyme Topoisomerase II. Teniposide ( Vumon, VM-26) is a chemotherapeutic Medication mainly used in the treatment of childhood Acute lymphocytic leukemia. These are semisynthetic derivatives of epipodophyllotoxins, alkaloids naturally occurring in the root of American Mayapple (Podophyllum peltatum). Epipodophyllotoxins are Alkaloids naturally occurring in the root of American Mayapple plant ( Podophyllum peltatum) Podophyllum peltatum (the mayapple is a Herbaceous Perennial plant in the family Berberidaceae, native to the eastern part of North

Antitumour antibiotics (L01D)

See main article: antineoplastic

The most important immunosuppressant from this group is dactinomycin, which is used in kidney transplantations. Antineoplastics (or "antitumor antibiotics" or "noncovalent DNA-binding drugs" or " Cytotoxic antibiotics" see also Neoplastics are Actinomycin is any of a class of Polypeptide antibiotics isolated from soil Bacteria of the genus Streptomyces. Kidney transplantation or renal transplantation is the Organ transplant of a Kidney in a patient with End-stage renal disease.

Monoclonal antibodies

Monoclonal antibodies work by targeting tumour specific antigens, thus enhancing the host's immune response to tumour cells to which the agent attaches itself. Monoclonal antibodies ( mAb or moAb) are monospecific antibodies that are identical because they are produced by one type of immune cell Examples are trastuzumab (Herceptin), cetuximab, and rituximab (Rituxan or Mabthera). Trastuzumab (more commonly known under the Trade Cetuximab (IMC-C225 -- marketed under the name Erbitux) is a chimeric Monoclonal antibody, an Epidermal growth factor receptor (EGFR inhibitor Rituximab, sold under the trade names Rituxan, MabThera and Reditux, is a chimeric Monoclonal antibody against the protein CD20 Bevacizumab (Avastin) is a monoclonal antibody that does not directly attack tumor cells but instead blocks the formation of new tumor vessels. Bevacizumab (Avastin Genentech/Roche is a Monoclonal antibody against Vascular endothelial growth factor (VEGF

Hormonal therapy

Several malignancies respond to hormonal therapy. Hormone therapy, or hormonal therapy is the use of Hormones in medical treatment Strictly speaking, this is not chemotherapy. Cancer arising from certain tissues, including the mammary and prostate glands, may be inhibited or stimulated by appropriate changes in hormone balance.

• Steroids (often dexamethasone) can inhibit tumour growth or the associated edema (tissue swelling), and may cause regression of lymph node malignancies. A steroid is a Terpenoid Lipid characterized by a Carbon skeleton with four fused rings generally arranged in a 6-6-6-5 fashion Dexamethasone is a potent synthetic member of the glucocorticoid class of Steroid Hormones It acts as an Anti-inflammatory and immunosuppressant Oedema (or Edema in American English formerly known as dropsy or hydropsy, is the increase of Interstitial fluid in any organ &mdash swelling Dexamethasone is also an antiemetic, so it may be used with cytotoxic chemotherapy even if it has no direct effect on the cancer. An anti-emetic is a drug that is effective against Vomiting and Nausea.
• Prostate cancer is often sensitive to finasteride, an agent that blocks the peripheral conversion of testosterone to dihydrotestosterone. Finasteride (marketed as Proscar, Propecia, Fincar, Finpecia, Finax, Finast, Finara, Finalo, Testosterone is a Steroid hormone from the Androgen group In mammals testosterone is primarily secreted in the testes of males and the Ovaries Dihydrotestosterone ( DHT) (Full name 5α-Dihydrotestosterone, abbreviating to 5α-DHT; INN: androstanolone; commonly called
• Breast cancer cells often highly express the estrogen and/or progesterone receptor. Breast cancer is a Cancer that starts in the cells of the Breast in women and men Estrogens (US otherwise oestrogens or œstrogens) are a group of Steroid compounds named for their importance in the Estrous cycle, Progesterone is a C-21 Steroid Hormone involved in the Female Menstrual cycle, Pregnancy (supports Gestation Inhibiting the production (with aromatase inhibitors) or action (with tamoxifen) of these hormones can often be used as an adjunct to therapy. Aromatase inhibitors ( AI) are a class of drugs used in the treatment of Breast cancer and Ovarian cancer in postmenopausal women that Tamoxifen is an orally active Selective estrogen receptor modulator (SERM that is used in the treatment of Breast cancer and is currently the world's largest
• Gonadotropin-releasing hormone agonists (GnRH), such as goserelin possess a paradoxical negative feedback effect followed by inhibition of the release of FSH (follicle-stimulating hormone) and LH (luteinizing hormone), when given continuously. Goserelin Acetate is an injectable Gonadotropin releasing hormone super-agonist ( GnRH agonist) also known as an LHRH agonist Follicle-stimulating hormone ( FSH) is a Hormone synthesized and secreted by Gonadotropes in the Anterior pituitary gland. Luteinizing hormone ( LH, also known as lutropin) is a Hormone produced by the Anterior pituitary gland.

Some other tumours are also hormone dependent, although the specific mechanism is still unclear. Hormones (from Greek ὁρμή - "impetus" are chemicals released by cells that affect cells in other parts of the body

Dosage

Dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, while at excessive doses the toxicity (side-effects, neutropenia) will be intolerable to the patient. Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is This has led to the formation of detailed "dosing schemes" in most hospitals, which give guidance on the correct dose and adjustment in case of toxicity. In immunotherapy, they are in principle used in smaller dosages than in the treatment of malignant diseases.

In most cases, the dose is adjusted for the patient's body surface area, a measure that correlates with blood volume. In Physiology and Medicine, the body surface area (BSA is the measured or calculated surface of a Human body. The BSA is usually calculated with a mathematical formula or a nomogram, using a patient's weight and height, rather than by direct measurement. This article is about the graphical devices called nomograms For a description of the Japanese puzzle see Nonogram.

Delivery

Most chemotherapy is delivered intravenously, although there are a number of agents that can be administered orally (e. In Pharmacology and Toxicology, a route Intravenous therapy or IV therapy is the giving of Liquid substances directly into a Vein. g. melphalan, busulfan, capecitabine). Melphalan hydrochloride (trade name Alkeran) is a Chemotherapy drug belonging to the class of Nitrogen mustard alkylating agents Busulfan is a Chemotherapy drug that is a cell cycle non-specific alkylating agent (slows the growth of cancer cells Capecitabine ( INN) (keɪpˈsaɪtəbiːn is an orally-administered chemotherapeutic agent used in the treatment of Metastatic breast and Colorectal In some cases, isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used. Isolated limb perfusion is a chemotherapeutic technique used to deliver high doses of cancer drugs directly into the bloodstream Melanoma is a Malignant Tumor of Melanocytes which are found predominantly in skin but also in the Bowel and the Eye (see The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumour sites without causing overwhelming systemic damage.

Depending on the patient, the cancer, the stage of cancer, the type of chemotherapy, and the dosage, intravenous chemotherapy may be given on either an inpatient or outpatient basis. A patient is any person who receives medical attention care or treatment. A patient is any person who receives medical attention care or treatment. For continuous, frequent or prolonged intravenous chemotherapy administration, various systems may be surgically inserted into the vasculature to maintain access. Commonly used systems are the Hickman line, the Port-a-Cath or the PICC line. A Hickman line is an Intravenous catheter most often used for the administration of Chemotherapy or other medications as well as for the withdrawal of In Medicine, a port (or portacath) is a small medical appliance that is installed beneath the skin A peripherally inserted central catheter ( PICC or PIC line) is a form of Intravenous access that can be used for a prolonged period of time e These have a lower infection risk, are much less prone to phlebitis or extravasation, and abolish the need for repeated insertion of peripheral cannulae. Phlebitis is an Inflammation of a Vein, usually in the Legs When phlebitis is associated with the formation of Blood clots ( Thrombosis

Harmful and lethal toxicity from chemotherapy limits the dosage of chemotherapy that can be given. Some tumours can be destroyed by sufficiently high doses of chemotheraputic agents. Unfortunately, these high doses cannot be given because they would be fatal to the patient.

Newer and experimental approaches

Hematopoietic stem cell transplant approaches

Stem cell harvesting and autologous or allogeneic stem cell transplant has been used to allow for higher doses of chemotheraputic agents where dosages are primarily limited by hematopoietic damage. Years of research in treating solid tumors, particularly breast cancer, with hematopoeitic stem cell transplants, has yielded little proof of efficacy. Hematological malignancies such as myeloma, lymphoma, and leukemia remain the main indications for stem cell transplants. Blood is a specialized Bodily fluid that delivers necessary substances to the body's cells ��such as nutrients and oxygen—and transports Waste products Multiple myeloma (also known as MM, myeloma, plasma cell myeloma, or as Kahler's disease after Otto Kahler) is a type of Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) Leukemia or leukaemia (Greek leukos λευκός, "white" aima αίμα, "blood" is a Cancer of the Blood

Isolated infusion approaches

Isolated limb perfusion (often used in melanoma), or isolated infusion of chemotherapy into the liver or the lung have been used to treat some tumours. Isolated limb perfusion is a chemotherapeutic technique used to deliver high doses of cancer drugs directly into the bloodstream Melanoma is a Malignant Tumor of Melanocytes which are found predominantly in skin but also in the Bowel and the Eye (see The main purpose of these approaches is to deliver a very high dose of chemotherapy to tumor sites without causing overwhelming systemic damage. These approaches can help control solitary or limited metastases, but they are by definition not systemic and therefore do not treat distributed metastases or micrometastases. Micrometastasis is a form of Metastasis (the spread of a cancer from its primary location to a distant site in which secondary tumors are too minuscule to be detected

Targeted delivery mechanisms

Specially targeted delivery vehicles aim to increase effective levels of chemotherapy for tumor cells while reducing effective levels for other cells. This should result in an increased tumor kill and/or reduced toxicity.

Specially targeted delivery vehicles have a differentially higher affinity for tumor cells by interacting with tumor specific or tumour associated antigens.

In addition to their targeting component, they also carry a payload - whether this is a traditional chemotherapeutic agent, or a radioisotope or an immune stimulating factor. Specially targeted delivery vehicles vary in their stability, selectivity and choice of target, but in essence they all aim to increase the maximum effective dose that can be delivered to the tumor cells. Reduced systemic toxicity means that they can also be used in sicker patients, and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches.

Nanoparticles

Nanoparticles have emerged as a useful vehicle for poorly-soluble agents such as paclitaxel. In Nanotechnology, a particle is defined as a small object that behaves as a whole unit in terms of its transport and properties Paclitaxel is a Mitotic inhibitor used in Cancer Chemotherapy. Protein-bound paclitaxel (e. Protein-bound paclitaxel is an Injectable formulation of Paclitaxel, a Mitotic inhibitor drug used in the treatment of Breast cancer g. Abraxane) or nab-paclitaxel was approved by the US FDA in January 2005 for the treatment of refractory breast cancer, and allows reduced use of the Cremophor vehicle usually found in paclitaxel. Breast cancer is a Cancer that starts in the cells of the Breast in women and men Cremophor EL is the registered trademark of BASF Corp for its version of polyethoxylated castor oil Nanoparticles made of magnetic material can also be used to concentrate agents at tumour sites using an externally applied magnetic field.

Side-effects

The treatment can be physically exhausting for the patient. Current chemotherapeutic techniques have a range of side effects mainly affecting the fast-dividing cells of the body. Important common side-effects include (dependent on the agent):

Immunosuppression and myelosuppression

Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells and platelets. Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the In Medicine, diarrhea, also spelled diarrhoea (see spelling differences) is frequent loose or liquid Bowel movements Acute diarrhea Constipation, costiveness, or irregularity, is a condition of the Digestive system in which a person (or animal experiences hard Feces that Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Malnutrition is a general term for a medical condition caused by an improper or insufficient diet. Alopecia or hair loss is the medical description of the loss of hair from the head or body sometimes to the extent of Baldness. Memory loss can have many causes Alzheimer's disease is an illness which can cause mild to severe memory loss An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor An infection is the detrimental Colonization of a host Organism by a foreign Species. Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a Systemic inflammatory response syndrome or SIRS caused Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from A secondary neoplasm refers to any of a class of Cancerous Tumors that are either metastatic offshoots of a primary tumor or apparently unrelated tumors Cardiotoxicity is the occurrence of heart muscle damage The heart becomes weaker and is not as efficient in pumping and therefore circulating blood Drug metabolism in liver The human body identifies almost all drugs as foreign substances (i Nephrotoxicity (from Greek nephros "kidney" is a Poisonous effect of some substances both Toxic chemicals and Medication, on the Kidney Ototoxicity is damage of the Ear ( oto) specifically the Cochlea or auditory nerve and sometimes the Vestibulum, by a Toxin An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor Bone marrow is the flexible tissue found in the hollow interior of Bones In adults marrow in large bones produces new Blood cells It constitutes 4% of Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Platelets, or Thrombocytes, are small cytoplasmic bodies derived from cells They circulate in the Blood of Mammals and are involved The latter two, when they occur, are improved with blood transfusion. Blood transfusion is the process of transferring Blood or blood-based products from one person into the Circulatory system of another Neutropenia (a decrease of the neutrophil granulocyte count below 0. Neutropenia (adjective neutropenic) from Latin Prefix neutro- and Greek Suffix -πενία (deficiency is Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the 5 x 10⁹/litre) can be improved with synthetic G-CSF (granulocyte-colony stimulating factor, e. The litre or liter (see spelling differences) is a unit of Volume. Granulocyte colony-stimulating factor ( G-CSF or GCSF) is a Colony-stimulating factor hormone Granulocytes are a category of White blood cells characterised by g. filgrastim, lenograstim, Neupogen, Neulasta). Filgrastim is a Granulocyte colony-stimulating factor (G-CSF analog used to stimulate the proliferation and differentiation of Granulocytes It is produced by Lenograstim is a Recombinant Granulocyte colony-stimulating factor which functions as a Immunostimulator.

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells which produce white and red blood cells) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. Bone marrow suppression or myelotoxicity (adjective myelotoxic) is a serious side-effect of Chemotherapy and certain drugs affecting the immune system Stem cells are cells found in most if not all multi-cellular Organisms. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood In Biology, autologous refers to cells, tissues or even Proteins that are reimplanted in the same individual as they come from (In autologous BMTs, cells are removed from the patient before the treatment, multiplied and then re-injected afterwards; in allogenic BMTs the source is a donor. ) However, some patients still develop diseases because of this interference with bone marrow.

Nausea and vomiting

Nausea and vomiting caused by chemotherapy; stomach upset may trigger a strong urge to vomit, or forcefully eliminate what is in the stomach. Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the

Stimulation of the vomiting center results in the coordination of responses from the diaphragm, salivary glands, cranial nerves, and gastrointestinal muscles to produce the interruption of respiration and forced expulsion of stomach contents known as retching and vomiting. The vomiting center is stimulated directly by afferent input from the vagal and splanchnic nerves, the pharynx, the cerebral cortex, cholinergic and histamine stimulation from the vestibular system, and efferent input from the chemoreceptor trigger zone (CTZ). The CTZ is in the area postrema, outside the blood-brain barrier, and is thus susceptible to stimulation by substances present in the blood or cerebral spinal fluid. The neurotransmitters dopamine and serotonin stimulate the vomiting center indirectly via stimulation of the CTZ.

The 5-HT₃ inhibitors are the most effective antiemetics and constitute the single greatest advance in the management of nausea and vomiting in patients with cancer. An anti-emetic is a drug that is effective against Vomiting and Nausea. These drugs are designed to block one or more of the signals that cause nausea and vomiting. The most sensitive signal during the first 24 hours after chemotherapy appears to be 5-HT₃. Blocking the 5-HT₃ signal is one approach to preventing acute emesis (vomiting), or emesis that is severe, but relatively short-lived. Approved 5-HT₃ inhibitors include: Dolasetron (Anzemet), Granisetron (Kytril), and Ondansetron (Zofran). Dolasetron (trade name Anzemet) is a Serotonin 5-HT3 receptor antagonist used to treat Nausea and Vomiting following Granisetron is a Serotonin 5-HT3 receptor antagonist used as an Antiemetic to treat Nausea and Vomiting following Ondansetron ( INN) (ɒnˈdænsɛtrɒn or Zofran is a Serotonin 5-HT3 receptor antagonist used mainly as an Antiemetic to The newest 5-HT₃ inhibitor, palonosetron (Aloxi), also prevents delayed nausea and vomiting, which occurs during the 2-5 days after treatment. Palonosetron ( INN, trade name Aloxi) is a 5-HT3 antagonist used in the prevention and treatment of Chemotherapy -induced Nausea

Another drug to control nausea in cancer patients became available in 2005. The substance P inhibitor aprepitant (marketed as Emend) has been shown to be effective in controlling the nausea of cancer chemotherapy. In Neuroscience, Substance P is a Neuropeptide: a short-chain Polypeptide that functions as a Neurotransmitter and as a Neuromodulator Aprepitant is a chemical compound that belongs to a class of drugs called Substance P antagonists (SPA The results of two large controlled trials were published in 2005, describing the efficacy of this medication in over 1,000 patients. ^[6]

Some studies^[7] and patient groups claim that the use of cannabinoids derived from marijuana during chemotherapy greatly reduces the associated nausea and vomiting, and enables the patient to eat. Cannabinoids ( are a group of terpeno[[phenol]]ic compounds present in Cannabis ( Cannabis sativa L Cannabis ( Cán-na-bis) is a Genus of Flowering plants that includes three putative species Cannabis sativa subsp Some synthetic derivatives of the active substance in marijuana (Tetrahydrocannabinol or THC) such as Marinol may be practical for this application. Natural marijuana, known as medical cannabis is also used and recommended by some oncologists, though its use is regulated and not everywhere legal[1] though there are sufficient studies to prove its efficacy. Medical cannabis refers to the use of the Cannabis plant as a physician-recommended Herbal therapy as well as synthetic THC and Cannabinoids

Other side effects

In particularly large tumors, such as large lymphomas, some patients develop tumor lysis syndrome from the rapid breakdown of malignant cells. Lymphoma a type of Neoplasm that originates in Lymphocytes (a type of White blood cell in the vertebrate Immune system) In Medicine ( Oncology and Hematology) tumor lysis syndrome ( TLS) is a group of metabolic complications that can occur after treatment Although prophylaxis is available and is often initiated in patients with large tumors, this is a dangerous side-effect which can lead to death if left untreated.

A proportion of patients report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, colloquially referred to as "chemo brain" by patients' groups. Post-chemotherapy cognitive impairment (also known as chemotherapy-induced cognitive dysfunction, chemo brain or chemo fog) describes the Cognitive ^[8]

Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and g. , doxorubicin), interstitial lung disease (e. Doxorubicin ( INN,; trade name Adriamycin; also known as hydroxydaunorubicin) is a drug used in cancer Chemotherapy. Interstitial lung disease (ILD, also known as diffuse parenchymal lung disease (DPLD, refers to a group of Lung diseases affecting the Interstitium g. , bleomycin) and occasionally secondary neoplasm (e. Bleomycin is a Glycopeptide antibiotic produced by the Bacterium Streptomyces verticillus. A secondary neoplasm refers to any of a class of Cancerous Tumors that are either metastatic offshoots of a primary tumor or apparently unrelated tumors g. MOPP therapy for Hodgkin's disease). MOPP is a medical Acronym describing the first combination Chemotherapy regimen that treated Hodgkin's disease with a high success rate

See also

• Cancer
• Gene therapy
• Experimental cancer treatments
• Chemotherapy regimens
• National Comprehensive Cancer Network
• Safe Handling of Hazardous Drugs

References

External links

• American Cancer Society - Chemotherapy
• Cancerbackup - Understanding Chemotherapy
• The leukemia and lymphoma society
• Chemotherapy.com Educational and support information about chemotherapy and associated side effects

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