hematology and oncology
Systemic Cancer Therapy
Chemotherapy
Cytotoxic drugs damage DNA and kill many normal cells as well as cancer cells. Antimetabolites such asfluorouracilandmethotrexateare cell cycle–specific and have a nonlinear dose-response relationship. In contrast, other drugs (eg, DNA cross-linkers, also known as alkylating agents) have a linear dose-response relationship, killing more cancer cells at higher doses. At high doses, DNA cross-linkers damage the bone marrow. Single drugs may cure selected cancers (eg, choriocarcinoma, hairy cell leukemia). More commonly, multidrug regimens incorporating drugs with different mechanisms of action and different toxicities are used to increase efficacy, reduce dose-related toxicity, and decrease the probability of drug resistance. These regimens result in substantial cure rates (eg, in acute leukemia, testicular cancer, lymphomas, and, less commonly, solid cancers such as lung and nasopharyngeal cancers). Multidrug regimens typically are given as repetitive cycles of a fixed combination of drugs. The interval between cycles should be the shortest one that allows recovery of normal tissues. Continuous infusion may increase cell kill with some cell cycle–specific drugs (eg,fluorouracil). For each patient, the probability of adverse effects should be weighed against the likelihood of benefit. End-organ function should be assessed before giving drugs with organ-specific toxicities. Dose modification or exclusion of certain drugs may be necessary in patients with lung disease (eg,bleomycin), kidney failure (eg,methotrexate), liver dysfunction (eg, taxanes) or heart disease (daunorubicin,cyclophosphamide). Despite these precautions, adverse effects commonly result from cytotoxic chemotherapy. The normal tissues most commonly affected are those with the highest intrinsic turnover rate: bone marrow, hair follicles, and the gastrointestinal epithelium. Imaging (CT, MRI, PET) is frequently done after 2 to 3 cycles of therapy to evaluate response. Therapy continues in responders or patients with stable disease. In patients whose cancer progresses, the regimen is often changed or stopped. 