cabinet that is designed to decrease worker exposure. additionally, it recommends training of all staff, the use of cabinets, implementing an initial evaluation of the technique of the safety program, and wearing protective gloves and gowns when opening drug packaging, handling vials, or labeling. when wearing personal protective equipment, one should inspect gloves for physical defects before use and always wear double gloves and protective gowns. health care workers are also required to wash their hands with water and soap before and after working with antineoplastic drugs, change gloves every 30 minutes or whenever punctured, and discard them immediately in a chemotherapy waste container. the gowns used should be disposable gowns made of polyethylene-coated polypropylene. when wearing gowns, individuals should make sure that the gowns are closed and have long sleeves. when preparation is done, the final product should be completely sealed in a plastic bag. the health care worker should also wipe all waste containers inside the ventilated cabinet before removing them from the cabinet. finally, workers should remove all protective wear and put them in a bag for their disposal inside the ventilated cabinet. administration drugs should only be administered using protective medical devices such as needle lists and closed systems and techniques such as priming of iv tubing by pharmacy personnel inside a ventilated cabinet. workers should always wear personal protective equipment such as double gloves, goggles, and protective gowns when opening the outer bag and assembling the delivery system to deliver the drug to the patient, and when disposing of all material used in the administration of the drugs. hospital workers should never remove tubing from an iv bag that contains an antineoplastic drug, and when disconnecting the tubing in the system, they should make sure the tubing has been thoroughly flushed. after removing the iv bag, the workers should place it together with other disposable items directly in the yellow chemotherapy waste container with the lid closed. protective equipment should be removed and put into a disposable chemotherapy waste container. after this has been done, one should double bag the chemotherapy waste before or after removing one's inner gloves. moreover, one must always wash one's hands with soap and water before leaving the drug administration site. employee training all employees whose jobs in health care facilities expose them to hazardous drugs must receive training. training should include shipping and receiving personnel, housekeepers, pharmacists, assistants, and all individuals involved in the transportation and storage of antineoplastic drugs. these individuals should receive information and training to inform them of the hazards of the drugs present in their areas of work. they should be informed and trained on operations and procedures in their work areas where they can encounter hazards, different methods used to detect the presence of hazardous drugs and how the hazards are released, and the physical and health hazards of the drugs, including their reproductive and carcinogenic hazard potential. additionally, they should be informed and trained on the measures they should take to avoid and protect themselves from these hazards. this information ought to be provided when health care workers come into contact with the drugs, that is, perform the initial assignment in a work area with hazardous drugs. moreover, training should also be provided when new hazards emerge as well as when new drugs, procedures, or equipment are introduced. housekeeping and waste disposal when performing cleaning and decontaminating the work area where antineoplastic drugs are used, one should make sure that there is sufficient ventilation to prevent the buildup of airborne drug concentrations. when cleaning the work surface, hospital workers should use deactivation and cleaning agents before and after each activity as well as at the end of their shifts. cleaning should always be done using double protective gloves and disposable gowns. after employees finish up cleaning, they should dispose of the items used in the activity in a yellow chemotherapy waste container while still wearing protective gloves. after removing the gloves, they should thoroughly wash their hands with soap and water. anything that comes into contact or has a trace of the antineoplastic drugs, such as needles, empty vials, syringes, gowns, and gloves, should be put in the chemotherapy waste container. spill control a written policy needs to be in place in case of a spill of antineoplastic products. the policy should address the possibility of various sizes of spills as well as the procedure and personal protective equipment required for each size. a trained worker should handle a large spill and always dispose of all cleanup materials in the chemical waste container according to epa regulations, not in a yellow chemotherapy waste container. occupational monitoring a medical surveillance program must be established. in case of exposure, occupational health professionals need to ask for a detailed history and do a thorough physical exam. they should test the urine of the potentially exposed worker by doing a urine dipstick or microscopic examination, mainly looking for blood, as several antineoplastic drugs are known to cause bladder damage. urinary mutagenicity is a marker of exposure to antineoplastic drugs that was first used by falck and colleagues in 1979 and uses bacterial mutagenicity assays. apart from being nonspecific, the test can be influenced by extraneous factors such as dietary intake and smoking and is, therefore, used sparingly. however, the test played a significant role in changing the use of horizontal flow cabinets to vertical flow biological safety cabinets during the preparation of antineoplastic drugs because the former exposed health care workers to high levels of drugs. this changed the handling of drugs and effectively reduced workers' exposure to antineoplastic drugs. biomarkers of exposure to antineoplastic drugs commonly include urinary platinum, methotrexate, urinary cyclophosphamide and ifosfamide, and urinary metabolite of 5-fluorouracil. in addition to this, there are other drugs used to measure the drugs directly in the urine, although they are rarely used. a measurement of these drugs directly in one's urine is a sign of high exposure levels and that an uptake of the drugs is happening either through inhalation or dermally. available agents main article: list of antineoplastic agents there is an extensive list of antineoplastic agents. several classification schemes have been used to subdivide the medicines used for cancer into several different types. history main article: history of cancer chemotherapy sidney farber did pioneering work in chemotherapy. the first use of small-molecule drugs to treat cancer was in the early 20th century, although the specific chemicals first used were not originally intended for that purpose. mustard gas was used as a chemical warfare agent during world war i and was discovered to be a potent suppressor of hematopoiesis (blood production). a similar family of compounds known as nitrogen mustards were studied further during world war ii at the yale school of medicine. it was reasoned that an agent that damaged the rapidly growing white blood cells might have a similar effect on cancer. therefore, in december 1942, several people with advanced lymphomas (cancers of the lymphatic system and lymph nodes) were given the drug by vein, rather than by breathing the irritating gas. their improvement, although temporary, was remarkable. concurrently, during a military operation in world war ii, following a german air raid on the italian harbour of bari, several hundred people were accidentally exposed to mustard gas, which had been transported there by the allied forces to prepare for possible retaliation in the event of german use of chemical warfare. the survivors were later found to have very low white blood cell counts. after wwii was over and the reports declassified, the experiences converged and led researchers to look for other substances that might have similar effects against cancer. the first chemotherapy drug to be developed from this line of research was mustine. since then, many other drugs have been developed to treat cancer, and drug development has exploded into a multibillion-dollar industry, although the principles and limitations of chemotherapy discovered by the early researchers still apply. the term chemotherapy the word chemotherapy without a modifier usually refers to cancer treatment, but its historical meaning was broader. the term was coined in the early 1900s by paul ehrlich as meaning any use of chemicals to treat any disease (chemo- + -therapy), such as the use of antibiotics (antibacterial chemotherapy). ehrlich was not optimistic that effective chemotherapy drugs would be found for the treatment of cancer. the first modern chemotherapeutic agent was arsphenamine, an arsenic compound discovered in 1907 and used to treat syphilis. this was later followed by sulfonamides (sulfa drugs) and penicillin. in today's usage, the sense "any treatment of disease with drugs" is often expressed with the word pharmacotherapy. sales the top 10 best-selling (in terms of revenue) cancer drugs of 2013: no.2013 global salesinntrade namesmarketing authorization holderindications 1$7.78 billionrituximabrituxan, mabtheraroche, pharmstandardnon-hodgkin's lymphoma, cll 2$6.75 billionbevacizumabavastinrochecolorectal, lung, ovarian and brain cancer 3$6.56 billiontrastuzumabherceptinrochebreast, esophagus and stomach cancer 4$4.69 billionimatinibgleevecnovartisleukemia, gi cancer 5$1.09 billionlenalidomiderevlimidcelgene, pharmstandardmultiple myeloma, mantle cell lymphoma 6$2.7 billionpemetrexedalimtaeli lillylung cancer 7$2.6 billionbortezomibvelcadejohnson & johnson, takeda, pharmstandardmultiple myeloma 8$1.87 billioncetuximaberbituxmerck kgaa, bristol-myers squibbcolon and head and neck cancer 9$1.73 billionleuprorelinlupron, eligardabbvie and takeda; sanofi and astellas pharmaprostate and ovarian cancer 10$1.7 billionabirateronezytigajohnson & johnsonprostate cancer research scanning electron micrograph of mesoporous silica, a type of nanoparticle used in the delivery of chemotherapeutic drugs main article: experimental cancer treatments targeted delivery vehicles 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 or reduced toxicity or both. antibody-drug conjugates antibody-drug conjugates (adcs) comprise an antibody, drug and a linker between them. the antibody will be targeted at a preferentially expressed protein in the tumour cells (known as a tumor antigen) or on cells that the tumor can utilise, such as blood vessel endothelial cells. they bind to the tumor antigen and are internalised, where the linker releases the drug into the cell. these 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 people who are sicker and that they can carry new chemotherapeutic agents that would have been far too toxic to deliver via traditional systemic approaches. the first approved drug of this type was gemtuzumab ozogamicin (mylotarg), released by wyeth (now pfizer). the drug was approved to treat acute myeloid leukemia. two other drugs, trastuzumab emtansine and brentuximab vedotin, are both in late clinical trials, and the latter has been granted accelerated approval for the treatment of refractory hodgkin's lymphoma and systemic anaplastic large cell lymphoma. nanoparticles nanoparticles are 1–1000 nanometer (nm) sized particles that can promote tumor selectivity and aid in delivering low-solubility drugs. nanoparticles can be targeted passively or actively. passive targeting exploits the difference between tumor blood vessels and normal blood vessels. blood vessels in tumors are "leaky" because they have gaps from 200 to 2000 nm, which allow nanoparticles to escape into the tumor. active targeting uses biological molecules (antibodies, proteins, dna and receptor ligands) to preferentially target the nanoparticles to the tumor cells. there are many types of nanoparticle delivery systems, such as silica, polymers, liposomes and magnetic particles. nanoparticles made of magnetic material can also be used to concentrate agents at tumor sites using an externally applied magnetic field. they have emerged as a useful vehicle in magnetic drug delivery for poorly soluble agents such as paclitaxel. electrochemotherapy electrochemotherapy is the combined treatment in which injection of a chemotherapeutic drug is followed by application of high-voltage electric pulses locally to the tumor. the treatment enables the chemotherapeutic drugs, which otherwise cannot or hardly go through the membrane of cells (such as bleomycin and cisplatin), to enter the cancer cells. hence, greater effectiveness of antitumor treatment is achieved. clinical electrochemotherapy has been successfully used for treatment of cutaneous and subcutaneous tumors irrespective of their histological origin. the method has been reported as safe, simple and highly effective in all reports on clinical use of electrochemotherapy. according to the esope project (european standard operating procedures of electrochemotherapy), the standard operating procedures (sop) for electrochemotherapy were prepared, based on the experience of the leading european cancer centres on electrochemotherapy. recently, new electrochemotherapy