QUESTION = Why does chemotherapy work if it's basically just pumping poison into your body? Why don't we often die from that poison? GENERATION = They do kill us all. The problem is that chemotherapy has side effects that shorten your life, which are usually side effects of fast acting chemicals that are only used in very dire situations, and often poison whole races. So there is no real selection pressure for the doctors to try and push treatments that have no side effect on you - you can't use a cream to eliminate cancer. Also, the idea is that if a patient was to die of a particularly dangerous cancer, it would have a lower chance of causing death due to severe side effects than a treatment that had a very high chance of killing the patient. And then there is the problem that sometimes people have cancer, but have a strong immune system, and are just lucky that they didn't get cancer when they were young. That could kill them right now because the Chemo just made them sick and can't do anything about it. It is important to understand that many chemicals are known to be poisonous if eaten or inhaled, and not all of them are toxic if swallowed or inhaled. So medicine might be making predictions that it is safe RETRIEVAL #0 = Chemotherapy---parts of the kidney and the toxicity may be asymptomatic (only seen on blood or urine tests) or may cause acute renal failure. Ototoxicity (damage to the inner ear) is a common side effect of platinum based drugs that can produce symptoms such as dizziness and vertigo. Section::::Adverse effects.:Other side-effects. Less common side-effects include red skin (erythema), dry skin, damaged fingernails, a dry mouth (xerostomia), water retention, and sexual impotence. Some medications can trigger allergic or pseudoallergic reactions. Specific chemotherapeutic agents are associated with organ-specific toxicities, including cardiovascular disease (e.g., doxorubicin), interstitial lung disease (e.g., bleomycin) and occasionally secondary neoplasm (e.g., MOPP therapy for Hodgkin's disease). Hand-foot syndrome is another side effect to cytotoxic chemotherapy. Section::::Limitations. 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 RETRIEVAL #1 = History of cancer chemotherapy---the NCI and elsewhere.:Anthracyclines and epipodophyllotoxins. Other effective molecules also came from industry during the period of 1970 to 1990, including anthracyclines and epipodophyllotoxins — both of which inhibited the action of topoisomerase II, an enzyme crucial for DNA synthesis. Section::::Supportive care during chemotherapy. As is obvious from their origins, the above cancer chemotherapies are essentially poisons. Patients receiving these agents experienced severe side-effects that limited the doses which could be administered, and hence limited the beneficial effects. Clinical investigators realized that the ability to manage these toxicities was crucial to the success of cancer chemotherapy. Several examples are noteworthy. Many chemotherapeutic agents cause profound suppression of the bone marrow. This is reversible, but takes time to recover. Support with platelet and red-cell transfusions as well as broad-spectrum antibiotics in case of infection during this period is crucial to allow the patient to recover. Several practical factors are also worth mentioning. Most of these agents caused very severe nausea (termed chemotherapy-induced nausea and vomiting (CINV) in the literature) which, while not directly causing patient deaths, was unbearable at higher doses. The development of new drugs to prevent nausea (the prototype of RETRIEVAL #2 = Chemotherapy---the inside of the cells. Following this, high levels of uric acid, potassium and phosphate are found in the blood. High levels of phosphate induce secondary hypoparathyroidism, resulting in low levels of calcium in the blood. This causes kidney damage and the high levels of potassium can cause cardiac arrhythmia. Although prophylaxis is available and is often initiated in people with large tumors, this is a dangerous side-effect that can lead to death if left untreated. Section::::Adverse effects.:Organ damage. Cardiotoxicity (heart damage) is especially prominent with the use of anthracycline drugs (doxorubicin, epirubicin, idarubicin, and liposomal doxorubicin). The cause of this is most likely due to the production of free radicals in the cell and subsequent DNA damage. Other chemotherapeutic agents that cause cardiotoxicity, but at a lower incidence, are cyclophosphamide, docetaxel and clofarabine. Hepatotoxicity (liver damage) can be caused by many cytotoxic drugs. The susceptibility of an individual to liver damage can be altered by other factors such as the cancer itself, viral hepatitis, immunosuppression and nutritional deficiency. The liver damage can consist of damage to liver cells, hepatic sinusoidal syndrome ( RETRIEVAL #3 = Chemotherapy---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). 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. Section::::Occupational exposure and safe handling. In the 1970s, antineoplastic (chemotherapy) drugs were identified as hazardous, and the American Society of Health-System Pharmacists (ASHP) has since then introduced the concept of hazardous drugs after publishing a recommendation in 1983 regarding handling hazardous drugs. The adaptation of federal regulations came when the U.S. Occupational Safety and Health Administration (OSHA) first released its guidelines in 1986 and then updated them in 1996, 1999, and, most recently, 2006. The National Institute for Occupational Safety and Health (NIOSH) has been conducting an assessment in the workplace since then regarding these drugs. Occupational exposure to antineoplastic drugs has been linked to multiple health effects, including infertility and possible carcinogenic effects. A few cases have been reported by the NIOSH alert report, such as one in which a female pharmacist was diagnosed with papillary transitional cell carcino RETRIEVAL #4 = Chemotherapy---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. 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. Section::::Cytotoxics and targeted therapies. Targeted therapies are a relatively new class of cancer drugs that can overcome many of the issues seen with the use of cytotoxics. RETRIEVAL #5 = Chemotherapy---sense, most chemotherapeutic drugs work by impairing mitosis (cell division), effectively targeting fast-dividing cells. As these drugs cause damage to cells, they are termed "cytotoxic". They prevent mitosis by various mechanisms including damaging DNA and inhibition of the cellular machinery involved in cell division. One theory as to why these drugs kill cancer cells is that they induce a programmed form of cell death known as apoptosis. As chemotherapy affects cell division, tumors with high growth rates (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. Malignancies with slower growth rates, such as indolent lymphomas, tend to respond to chemotherapy much more modestly. Heterogeneic tumours may also display varying sensitivities to chemotherapy agents, depending on the subclonal populations within the tumor. Cells from the immune system also make crucial contributions to the antitumor effects of chemotherapy. For example, the chemotherapeutic drugs oxaliplatin and cyclophosphamide can cause tumor cells to die in a way that is detectable by the immune system (called immunogenic cell death), which mobilizes RETRIEVAL #6 = Low-dose chemotherapy---Low-dose chemotherapy Low-dose chemotherapy is being studied/used in the treatment of cancer to avoid the side effects of conventional chemotherapy. Historically, oncologists have used the highest possible dose that the body can tolerate in order to kill as many cancer cells as possible. After high-dose treatments, the body reacts, sometimes quite severely. Infections from external causes become a leading threat of death. Section::::Forms of low-dose chemotherapy. The following forms of low-dose chemotherapy have been proposed. They are not always widely available treatments at hospitals. Section::::Forms of low-dose chemotherapy.:Oral low-dose chemotherapy. Patients are given chemotherapy drugs orally very frequently. This approach can be very effective for some cancers and can minimize side effects for some people. More patients are using oral chemotherapy than ever before. Section::::Forms of low-dose chemotherapy.:Low-dose chemotherapy and antiangiogenesis. Adam Dicker, an associate professor at Jefferson Medical College of Thomas Jefferson University in Philadelphia, supports that chemotherapy is often used in the highest possible doses. They are rethinking chemotherapy because of the antiangiogenic effects