Chemotherapy agents are grouped into different categories based on mechanism of action. These categories include alkylating agents, antimicrotubule agents, plant alkaloids, antimetabolites, anthracyclines, topoisomerase inhibitors, and others.
In addition to tumor site and diagnosis, individual patient factors such as age, organ function, comorbidities, and residual toxicities from the receipt of prior therapies will all influence the choice of chemotherapy regimens. Dose adjustments should be made when appropriate depending on goals of treatment and previous treatments the patient may have received. Physicians prescribing anticancer agents should understand the goals of care for the individual patient (curative vs. palliative) as well as the metabolism and toxicities of the agents prescribed. Patients and their families should be educated about the expected toxicities and goals of therapy.
Tumor growth is a complicated intricate process governed by genetic abnormalities within the cell and the tumor's interaction with its microenvironment. The understanding of cancer has accelerated significantly over the past decade, and Hanahan and Weinberg1 have defined the distinguishing features of cancer detailing the following hallmarks in addition to genomic instability as an underlying premise of the make-up of cancer cells: promotion and sustaining proliferative signaling, evading growth suppressors, resisting cell death, allowing replicative immortality, induction of angiogenesis, and activating invasion and metastasis. The proliferation and growth control of normal cells are not well understood, but the mitogenic signaling of cancer cells is increasingly better understood. Cancer cells acquire the ability to proliferate unchecked by several different mechanisms: self-production of growth factor ligands; control of the tumor microenvironment by signaling local stromal cells, which in turn produce factors leading to cancer growth; overexpression or enhanced signaling of transmembrane receptors; and growth factor independence via constitutive activation of tyrosine kinases within the receptor and/or downstream signaling molecules.2 Enabling characteristics of cancer cells that allow the above changes to occur include overall genomic instability and the cancer cell's ability to avoid immune destruction.3
Cell Kinetics and Log Kill Hypothesis
Cell kinetics were originally described based on murine tumor models, but it is now accepted that most human solid tumors do not grow in an exponential manner. The log kill hypothesis was based on the L1210 murine leukemia model, which is a fast-growing leukemia where 100% of the cells are actively progressing through the cell cycle.4 Logarithmic kill hypothesis states that a given anticancer drug should kill a constant proportion or fraction of cells in contrast to a constant number of cells, and cell kill is proportional regardless of the bulk of tumor. For example, if a drug can lead to a 3 log kill of cancer cells and can reduce the cancer burden from 109 to 106, the same drug and dose can also reduce the tumor burden from 106 to 103.