chemotherapy chemotherapy chemotherapy (often abbreviated to chemo and sometimes ctx or ctx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. chemotherapy may be given with a curative intent (which almost always involves combinations of drugs) or it may aim 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. this article is about the cancer treatment. for antimicrobial chemotherapy, see antimicrobial chemotherapy. for the journal, see chemotherapy (journal). chemotherapya woman being treated with docetaxel chemotherapy for breast cancer. cold mittens and cold booties are placed on her hands and feet to reduce harm to her nails.other nameschemo, ctx, ctx the term chemotherapy has come to connote non-specific usage of intracellular poisons to inhibit mitosis (cell division) or induce dna damage, which is why inhibition of dna repair can augment chemotherapy. the connotation of the word chemotherapy excludes more selective agents that block extracellular signals (signal transduction). the development of 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. by contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as targeted therapy. importantly, the use of drugs (whether chemotherapy, hormonal therapy or targeted therapy) constitutes systemic therapy for cancer in that they are introduced into the blood stream and are therefore in principle able to address cancer at any anatomic location in the body. systemic therapy is often used in conjunction with other modalities that constitute local therapy (i.e., treatments whose efficacy is confined to the anatomic area where they are applied) for cancer such as radiation therapy, surgery or hyperthermia therapy. 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 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. treatment strategies common combination chemotherapy regimens cancer type drugs acronym breast cancer cyclophosphamide, methotrexate, 5-fluorouracil, vinorelbinecmf doxorubicin, cyclophosphamideac hodgkin's lymphoma docetaxel, doxorubicin, cyclophosphamide tac doxorubicin, bleomycin, vinblastine, dacarbazine abvd mustine, vincristine, procarbazine, prednisolone mopp non-hodgkin's lymphoma cyclophosphamide, doxorubicin, vincristine, prednisolonechop, r-cvp germ cell tumor bleomycin, etoposide, cisplatinbep stomach cancer epirubicin, cisplatin, 5-fluorouracilecf epirubicin, cisplatin, capecitabineecx bladder cancer methotrexate, vincristine, doxorubicin, cisplatinmvac lung cancer cyclophosphamide, doxorubicin, vincristine, vinorelbinecav colorectal cancer 5-fluorouracil, folinic acid, oxaliplatinfolfox pancreatic cancer gemcitabine, 5-fluorouracilfolfox bone cancer doxorubicin, cisplatin, methotrexate, ifosfamide, etoposide map/mapie 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. induction chemotherapy is the first line treatment of cancer with a chemotherapeutic drug. this type of chemotherapy is used for curative intent.: 55–59 combined modality chemotherapy is the use of drugs with other cancer treatments, such as surgery, radiation therapy, or hyperthermia therapy. 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 intensification chemotherapy is identical to consolidation chemotherapy but a different drug than the induction chemotherapy is used.: 55–59 combination chemotherapy 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.: 55–59 : 17–18 neoadjuvant chemotherapy is given prior to a local treatment such as surgery, and is designed to shrink the primary tumor.: 55–59 it is also given for cancers with a high risk of micrometastatic disease.: 42 adjuvant chemotherapy 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.: 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. maintenance chemotherapy is a repeated low-dose treatment to prolong remission.: 55–59 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 all chemotherapy regimens require that the recipient be capable of undergoing the treatment. performance status is often used as a measure to determine whether a person can receive chemotherapy, or whether dose reduction is required. because only a fraction of the cells in a tumor die with each treatment (fractional kill), repeated doses must be administered to continue to reduce the size of the tumor. current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity. efficiency the efficiency of chemotherapy depends on the type of cancer and the stage. the overall effectiveness ranges from being curative for some cancers, such as some leukemias, to being ineffective, such as in some brain tumors, to being needless in others, like most non-melanoma skin cancers. dosage dose response relationship of cell killing by chemotherapeutic drugs on normal and cancer cells. at high doses the percentage of normal and cancer cells killed is very similar. for this reason, doses are chosen where anti-tumour activity exceeds normal cell death. dosage of chemotherapy can be difficult: if the dose is too low, it will be ineffective against the tumor, whereas, at excessive doses, the toxicity (side-effects) will be intolerable to the person receiving it. the standard method of determining chemotherapy dosage is based on calculated body surface area (bsa). the bsa is usually calculated with a mathematical formula or a nomogram, using the recipient's weight and height, rather than by direct measurement of body area. this formula was originally derived in a 1916 study and attempted to translate medicinal doses established with laboratory animals to equivalent doses for humans. the study only included nine human subjects. when chemotherapy was introduced in the 1950s, the bsa formula was adopted as the official standard for chemotherapy dosing for lack of a better option. the validity of this method in calculating uniform doses has been questioned because the formula only takes into account the individual's weight and height. drug absorption and clearance are influenced by multiple factors, including age, sex, metabolism, disease state, organ function, drug-to-drug interactions, genetics, and obesity, which have major impacts on the actual concentration of the drug in the person's bloodstream. as a result, there is high variability in the systemic chemotherapy drug concentration in people dosed by bsa, and this variability has been demonstrated to be more than ten-fold for many drugs. in other words, if two people receive the same dose of a given drug based on bsa, the concentration of that drug in the bloodstream of one person may be 10 times higher or lower compared to that of the other person. this variability is typical with many chemotherapy drugs dosed by bsa, and, as shown below, was demonstrated in a study of 14 common chemotherapy drugs. 5-fu dose management results in significantly better response and survival rates versus bsa dosing. the result of this pharmacokinetic variability among people is that many people do not receive the right dose to achieve optimal treatment effectiveness with minimized toxic side effects. some people are overdosed while others are underdosed. for example, in a randomized clinical trial, investigators found 85% of metastatic colorectal cancer patients treated with 5-fluorouracil (5-fu) did not receive the optimal therapeutic dose when dosed by the bsa standard—68% were underdosed and 17% were overdosed. there has been controversy over the use of bsa to calculate chemotherapy doses for people who are obese. because of their higher bsa, clinicians often arbitrarily reduce the dose prescribed by the bsa formula for fear of overdosing. in many cases, this can result in sub-optimal treatment. several clinical studies have demonstrated that when chemotherapy dosing is individualized to achieve optimal systemic drug exposure, treatment outcomes are improved and toxic side effects are reduced. in the 5-fu clinical study cited above, people whose dose was adjusted to achieve a pre-determined target exposure realized an 84% improvement in treatment response rate and a six-month improvement in overall survival (os) compared with those dosed by bsa. 5-fu dose management avoids serious side effects experienced with bsa dosing. 5-fu dose management in the folfox regimen increases treatment response significantly and improves survival by six months. in the same study, investigators compared the incidence of common 5-fu-associated grade 3/4 toxicities between the dose-adjusted people and people dosed per bsa. the incidence of debilitating grades of diarrhea was reduced from 18% in the bsa-dosed group to 4% in the dose-adjusted group and serious hematologic side effects were eliminated. because of the reduced toxicity, dose-adjusted patients were able to be treated for longer periods of time. bsa-dosed people were treated for a total of 680 months while people in the dose-adjusted group were treated for a total of 791 months. completing the course of treatment is an important factor in achieving better treatment outcomes. similar results were found in a study involving people with colorectal cancer who have been treated with the popular folfox regimen. the incidence of serious diarrhea was reduced from 12% in the bsa-dosed group of patients to 1.7% in the dose-adjusted group, and the incidence of severe mucositis was reduced from 15% to 0.8%. the folfox study also demonstrated an improvement in treatment outcomes. positive response increased from 46% in the bsa-dosed group to 70% in the dose-adjusted group. median progression free survival (pfs) and overall survival (os) both improved by six months in the dose adjusted group. one approach that can help clinicians individualize chemotherapy dosing is to measure the drug levels in blood plasma over time and adjust dose according to a formula or algorithm to achieve optimal exposure. with an established target exposure for optimized treatment effectiveness with minimized toxicities, dosing can be personalized to achieve target exposure and optimal results for each person. such an algorithm was used in the clinical trials cited above and resulted in significantly improved treatment outcomes. oncologists are already individualizing dosing of some cancer drugs based on exposure. carboplatin: 4 and busulfan dosing rely upon results from blood tests to calculate the optimal dose for each person. simple blood tests are also available for dose optimization of methotrexate, 5-fu, paclitaxel, and docetaxel. the serum albumin level immediately prior to chemotherapy administration is an independent prognostic predictor of survival in various cancer types. types two dna bases that are cross-linked by a nitrogen mustard. different nitrogen mustards will have different chemical groups (r). the nitrogen mustards most commonly alkylate the n7 nitrogen of guanine (as shown here) but other atoms can be alkylated. alkylating agents main article: alkylating antineoplastic agent alkylating agents are the oldest group of chemotherapeutics in use today. originally derived from mustard gas used in world war i, there are now many types of alkylating agents in use. they are so named because of their ability to alkylate many molecules, including proteins, rna and dna. this ability to bind covalently to dna via their alkyl group is the primary cause for their anti-cancer effects. dna is made of two strands and the molecules