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Chemotherapy

Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) in a standard regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim only to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology.[1][2]

This article is about the cancer treatment. For antimicrobial chemotherapy, see Antimicrobial chemotherapy. For the journal, see Chemotherapy (journal).

Chemotherapy

chemo, CTX, CTx

The term chemotherapy now means the non-specific use of intracellular poisons to inhibit mitosis (cell division) or to induce DNA damage (so that DNA repair can augment chemotherapy).[3] This meaning excludes the more-selective agents that block extracellular signals (signal transduction). Therapies with specific molecular or genetic targets, which inhibit growth-promoting signals from classic endocrine hormones (primarily estrogens for breast cancer and androgens for prostate cancer), are now called hormonal therapies. Other inhibitions of growth-signals, such as those associated with receptor tyrosine kinases, are targeted therapy.


The use of drugs (whether chemotherapy, hormonal therapy, or targeted therapy) is systemic therapy for cancer: they are introduced into the blood stream (the system) and therefore can treat cancer anywhere in the body. Systemic therapy is often used with other, local therapy (treatments that work only where they are applied), such as radiation, surgery, and hyperthermia.


Traditional chemotherapeutic agents are cytotoxic by means of interfering with cell division (mitosis) but cancer cells vary widely in their susceptibility to these agents. To a large extent, chemotherapy can be thought of as a way to damage or stress cells, which may then lead to cell death if apoptosis is initiated. Many of the side effects of chemotherapy can be traced to damage to normal cells that divide rapidly and are thus sensitive to anti-mitotic drugs: cells in the bone marrow, digestive tract and hair follicles. This results in the most common side-effects of chemotherapy: myelosuppression (decreased production of blood cells, hence that also immunosuppression), mucositis (inflammation of the lining of the digestive tract), and alopecia (hair loss). Because of the effect on immune cells (especially lymphocytes), chemotherapy drugs often find use in a host of diseases that result from harmful overactivity of the immune system against self (so-called autoimmunity). These include rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, vasculitis and many others.

Induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. This type of chemotherapy is used for curative intent.[6]: 55–59 

[1]

Combined modality chemotherapy is the use of drugs with other , such as surgery, radiation therapy, or hyperthermia therapy.

cancer treatments

Consolidation chemotherapy is given after remission in order to prolong the overall disease-free time and improve overall survival. The drug that is administered is the same as the drug that achieved remission.: 55–59 

[6]

Intensification chemotherapy is identical to consolidation chemotherapy but a different drug than the induction chemotherapy is used.: 55–59 

[6]

involves treating a person 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. Also, the drugs can often be used at lower doses, reducing toxicity.[6]: 55–59 [7]: 17–18 [5]

Combination chemotherapy

chemotherapy is given prior to a local treatment such as surgery, and is designed to shrink the primary tumor.[6]: 55–59  It is also given for cancers with a high risk of micrometastatic disease.[8]: 42 

Neoadjuvant

is given after a local treatment (radiotherapy or surgery). It can be used when there is little evidence of cancer present, but there is risk of recurrence.[6]: 55–59  It is also useful in killing any cancerous cells that have spread to other parts of the body. These micrometastases can be treated with adjuvant chemotherapy and can reduce relapse rates caused by these disseminated cells.[9]

Adjuvant chemotherapy

Maintenance chemotherapy is a repeated low-dose treatment to prolong remission.[6]: 55–59 

[5]

Salvage chemotherapy or palliative chemotherapy is given without curative intent, but simply to decrease tumor load and increase life expectancy. For these regimens, in general, a better toxicity profile is expected.: 55–59 

[6]

Limitations[edit]

Chemotherapy does not always work, and even when it is useful, it may not completely destroy the cancer. People frequently fail to understand its limitations. In one study of people who had been newly diagnosed with incurable, stage 4 cancer, more than two-thirds of people with lung cancer and more than four-fifths of people with colorectal cancer still believed that chemotherapy was likely to cure their cancer.[138]


The blood–brain barrier poses an obstacle to delivery of chemotherapy to the brain. This is because the brain has an extensive system in place to protect it from harmful chemicals. Drug transporters can pump out drugs from the brain and brain's blood vessel cells into the cerebrospinal fluid and blood circulation. These transporters pump out most chemotherapy drugs, which reduces their efficacy for treatment of brain tumors. Only small lipophilic alkylating agents such as lomustine or temozolomide are able to cross this blood–brain barrier.[139][140][141]


Blood vessels in tumors are very different from those seen in normal tissues. As a tumor grows, tumor cells furthest away from the blood vessels become low in oxygen (hypoxic). To counteract this they then signal for new blood vessels to grow. The newly formed tumor vasculature is poorly formed and does not deliver an adequate blood supply to all areas of the tumor. This leads to issues with drug delivery because many drugs will be delivered to the tumor by the circulatory system.[142]

Resistance[edit]

Resistance is a major cause of treatment failure in chemotherapeutic drugs. There are a few possible causes of resistance in cancer, one of which is the presence of small pumps on the surface of cancer cells that actively move chemotherapy from inside the cell to the outside. Cancer cells produce high amounts of these pumps, known as p-glycoprotein, in order to protect themselves from chemotherapeutics. Research on p-glycoprotein and other such chemotherapy efflux pumps is currently ongoing. Medications to inhibit the function of p-glycoprotein are undergoing investigation, but due to toxicities and interactions with anti-cancer drugs their development has been difficult.[143][144] Another mechanism of resistance is gene amplification, a process in which multiple copies of a gene are produced by cancer cells. This overcomes the effect of drugs that reduce the expression of genes involved in replication. With more copies of the gene, the drug can not prevent all expression of the gene and therefore the cell can restore its proliferative ability. Cancer cells can also cause defects in the cellular pathways of apoptosis (programmed cell death). As most chemotherapy drugs kill cancer cells in this manner, defective apoptosis allows survival of these cells, making them resistant. Many chemotherapy drugs also cause DNA damage, which can be repaired by enzymes in the cell that carry out DNA repair. Upregulation of these genes can overcome the DNA damage and prevent the induction of apoptosis. Mutations in genes that produce drug target proteins, such as tubulin, can occur which prevent the drugs from binding to the protein, leading to resistance to these types of drugs.[145] Drugs used in chemotherapy can induce cell stress, which can kill a cancer cell; however, under certain conditions, cells stress can induce changes in gene expression that enables resistance to several types of drugs.[146] In lung cancer, the transcription factor NFκB is thought to play a role in resistance to chemotherapy, via inflammatory pathways.[147][148][149]

Cytotoxics and targeted therapies[edit]

Targeted therapies are a relatively new class of cancer drugs that can overcome many of the issues seen with the use of cytotoxics. They are divided into two groups: small molecule and antibodies. The massive toxicity seen with the use of cytotoxics is due to the lack of cell specificity of the drugs. They will kill any rapidly dividing cell, tumor or normal. Targeted therapies are designed to affect cellular proteins or processes that are utilised by the cancer cells.[150] This allows a high dose to cancer tissues with a relatively low dose to other tissues. Although the side effects are often less severe than that seen of cytotoxic chemotherapeutics, life-threatening effects can occur. Initially, the targeted therapeutics were supposed to be solely selective for one protein. Now it is clear that there is often a range of protein targets that the drug can bind. An example target for targeted therapy is the BCR-ABL1 protein produced from the Philadelphia chromosome, a genetic lesion found commonly in chronic myelogenous leukemia and in some patients with acute lymphoblastic leukemia. This fusion protein has enzyme activity that can be inhibited by imatinib, a small molecule drug.[151][152][153][154]

Other uses[edit]

Some chemotherapy drugs are used in diseases other than cancer, such as in autoimmune disorders,[165] and noncancerous plasma cell dyscrasia. In some cases they are often used at lower doses, which means that the side effects are minimized,[165] while in other cases doses similar to ones used to treat cancer are used. Methotrexate is used in the treatment of rheumatoid arthritis (RA),[166] psoriasis,[167] ankylosing spondylitis[168] and multiple sclerosis.[169][170] The anti-inflammatory response seen in RA is thought to be due to increases in adenosine, which causes immunosuppression; effects on immuno-regulatory cyclooxygenase-2 enzyme pathways; reduction in pro-inflammatory cytokines; and anti-proliferative properties.[166] Although methotrexate is used to treat both multiple sclerosis and ankylosing spondylitis, its efficacy in these diseases is still uncertain.[168][169][170] Cyclophosphamide is sometimes used to treat lupus nephritis, a common symptom of systemic lupus erythematosus.[171] Dexamethasone along with either bortezomib or melphalan is commonly used as a treatment for AL amyloidosis. Recently, bortezomid in combination with cyclophosphamide and dexamethasone has also shown promise as a treatment for AL amyloidosis. Other drugs used to treat myeloma such as lenalidomide have shown promise in treating AL amyloidosis.[172]


Chemotherapy drugs are also used in conditioning regimens prior to bone marrow transplant (hematopoietic stem cell transplant). Conditioning regimens are used to suppress the recipient's immune system in order to allow a transplant to engraft. Cyclophosphamide is a common cytotoxic drug used in this manner and is often used in conjunction with total body irradiation. Chemotherapeutic drugs may be used at high doses to permanently remove the recipient's bone marrow cells (myeloablative conditioning) or at lower doses that will prevent permanent bone marrow loss (non-myeloablative and reduced intensity conditioning).[173] When used in non-cancer setting, the treatment is still called "chemotherapy", and is often done in the same treatment centers used for people with cancer.

Other animals[edit]

Chemotherapy is used in veterinary medicine similar to how it is used in human medicine.[208]

National Institute for Occupational Safety and Health

Hazardous Drug Exposures in Health Care

NIOSH List of Antineoplastic and Other Hazardous Drugs in Healthcare Settings, 2016, National Institute for Occupational Safety and Health