Chemotherapy agents

Fluorinated Heterocyclic Compounds. HeterocycHc compounds containing the CF group are prepared by methods similar to those used in the fluorination of aHphatic compounds. The direct action of fluorine on uracil yields the cancer chemotherapy agent, 5-fluorouracil [51-21-8] as one special example of a selective fluorination on a commercial scale (25). 

The development of injectable mictocapsules for deUvery of chemotherapy agents remains another active area of research. The ultimate goal is to achieve targeted deUvery of chemotherapy agents to specific sites in the body, ideaUy by injection of dmg-loaded mictocapsules that would seek out and destroy diseased ceUs. Intra-arterial infusion chemotherapy is a direct approach to targeted deUvery. The clinical appHcations of microspheres and mictocapsules in embolization and chemotherapy have been assessed (49) (see Chemotherapeutics, anticancer). 

MaePhee, M.J., Campagna, A., Best, A., Kidd, R. and Drohan, W., Fibrin sealant as a delivery vehicle for sustained and controlled release of chemotherapy agents. In Sierra, D. and Saltz, R. (Eds.), Surgical Adhesives and Sealants, Current Technology and Applications. Technomic, Lancaster, PA, 1996, pp. 145-154. 

The nitrogen mustards are cytotoxic chemotherapy agents which are chemically derived from mustard gas. Although their current use is medicinal, the predecessor of these compounds was also used for chemical warfare putposes. 

Because of the severe toxicities associated with many of the chemotherapy agents, safety precautions must be in place to prevent chemotherapy errors, accidental chemotherapy exposures, and overdosages. 

Carcinogenic agents include chemicals in the environment, such as aniline and benzene, which are associated with the development of bladder cancer and leukemia, respectively. Environmental factors, such as excessive sun exposure, also may result in cancer. Viruses, including the human papilloma virus and hepatitis B, maybe associated with the development of cancer. Some of the chemotherapy agents cause secondary cancers after therapy has been completed. Numerous factors may contribute to the development of cancer. 

Cancer chemotherapy and the treatment of cancers are analogous to anti-infectives and the treatment of infections. Cancer cells may be sensitive to certain chemotherapy agents, but then with repeated exposure, the cells become resistant to treatment. The resistant cells then grow and multiply. While tumors may be tested for chemotherapy sensitivity, this area is still developing. Today, tumor sensitivity can demonstrate tumor resistance so that needless exposure to an inadequate therapy and its toxicity can be avoided. 

Tumor cells may become resistant when genetic changes occur during cell proliferation. Resistant cancer cells with the mdr-1 gene may possess a membrane-associated protein, p-glycoprotein, that facilitates efflux of chemotherapy agents out of the cells. Numerous attempts at blocking this efflux pump have been unsuccessful. 

Many chemotherapy agents have significant organ toxicities that preclude using larger and larger doses to treat the cancer. The doses of chemotherapy must be spaced out to allow the patient to recover from the toxicity of the chemotherapy each... 

Another important consideration for treatment of cancers is reimbursement by third-party payors for off-label use of chemotherapy agents because of the high expense. The American Association of Cancer Centers (www.accc-cancer.org) provides... 

The alkylating drugs are the oldest category of chemotherapy agents. Globally, cytoxocity results from inhibition of DNA replication because interlinked strands do not separate. 

The rapidly proliferating cells of the GI tract make them susceptible to the effects of chemotherapy. Mucositis is the inflamed, ulcerated mucosa of the mouth, esophagus, and lower GI tract that may result in infection and pain with subsequent decreased fluid and nutritional intake. Methotrexate, 5-FU, etoposide, and doxorubicin are the chemotherapy agents most commonly associated with mucositis. Patients should be instructed on good oral mouth care and use saline rinses several... 

Capecitabine is an oral prodrug of 5-FU that also is effective in the adjuvant setting and is being evaluated as a replacement for 5-FU for patient convenience and safety reasons. Data suggest that capecitabine is at least equivalent to 5-FU and leucovorin in efficacy and is better tolerated by patients.24 Consequently, most practitioners feel that capecitabine is an acceptable alternative to IV 5-FU plus leucovorin. However, the role of capecitabine with additional chemotherapy agents such as oxaliplatin requires further study... 

TABLE 91-2. Summary of Chemotherapy Agents Used for First-Line Treatment of Advanced Ovarian Cancer Mechanism of action of first-line agents ... 

TABLE 91-3. Summary of Chemotherapy Agents Used for Second-Line Treatment of Progressive and Recurrent Platinum-Resistant Ovarian Cancer... 

Provide appropriate patient education on respective chemotherapy agents that will be given for treatment of recurrent ovarian cancer. 

Which chemotherapy agent(s) will JM receive is(are) considered to be vesicants Irritants Nonvesicants ... 

Therapeutic modalities to treat extravasation events consist of specific antidotes to halt or decrease the severity of local tissue necrosis. It should be noted that only one-third of extravasation events will lead to local tissue necrosis, and most studies of antidotes are in animal models or isolated case reports. Antidotes either disperse or bind the chemotherapy agent and accelerate the removal of the agent from the tissues. Specific antidotes and their uses are presented in Table 96-16. 

Extravasation Movement of fluid from inside a blood vessel into the surrounding tissues for example, leakage or infiltration of a vesicant chemotherapy agent into local tissue. 

Mucositis Inflammation of mucous membranes, typically within the oral and esophageal mucosa. Mucositis is usually associated with certain chemotherapy agents and radiation therapy involving mucosal areas. 

Colchicine (a drug used in treatment of gout) and vinblastine (a cancer chemotherapy agent) may decrease liver uptake of americium. In rats that received an intraperitoneal injection of either colchicine and vinblastine prior to an intravenous or intramuscular injection of americium citrate, liver uptake of americium was lower, relative to controls, and kidney and skeletal americium uptake were higher (Seidel 1984, 1985). The effect is thought to involve disruption of hepatic microtubule formation, which is critical to the formation and intracellular processing of lysosomes, the initial site of accumulation of americium in the liver. 

Taxol (K. C. Nicolaou) a potent cancer chemotherapy agent. 

Second, the book includes sections on pain control, antibiotic use in neutropenic fever, antiemetic guidelines, and supportive care medications. The book continues with a section on drugs used in commonly encountered problems in hematology, and concludes with a listing of the wholesale costs of most chemotherapy agents. The rapid growth of chemotherapeutic options will make frequent updates of this handbook essential for the future state-of-the-art care of our patients. 

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