Chemotherapy, the management of disease with chemical substances, is used to manage primary as well as recurrent cancers. It can be used in combination with other forms of treatment and can potentiate the effect of the other modality, such as radiation therapy. Chemotherapy is classified according to its relation to the temporal delivery of the primary modality. Neoadjuvant or induction chemotherapy is delivered before radiation therapy or a surgical procedure to attempt to decrease the tumor burden and make it more amenable to the primary therapy. Concomitant chemotherapy is given simultaneously with the definitive form of therapy. When used with radiation therapy, chemotherapy can act as a sensitizer to augment the radiation effect. Adjuvant chemotherapy is given after radiation or surgical treatment to help control remaining microscopic disease. In some malignant diseases such as leukemia and lymphoma, chemotherapy may be the primary therapy, whereas in head and neck cancer chemotherapy is provided in conjunction with a primary therapy.

One use of chemotherapy is palliation of the symptoms of metastatic or recurrent cancer. Despite response rates exceeding 75% with the use of induction chemotherapy, it has not been shown to improve survival rates. Although patients who have complete responses to chemotherapy have a better prognosis than those who do not respond, factors other than the chemotherapy seem to be responsible. At the very least, response to chemotherapy may correlate with better biologic behavior of the cancer or help identify patients with curable disease regardless of the primary method chosen (surgical or radiation therapy).

Chemotherapeutic drugs exert their effects by interfering with cell proliferation or the processes of DNA, RNA, or protein synthesis. This causes a proliferation crisis in cells that lack the capability to repair themselves. Because tumor cells are derived from normal cells it is difficult to design drugs that will selectively attack cancer cells yet spare normal cells. Cancer and normal cells differ mainly with regard to the regulation and rate of cell division. Most anticancer drugs indiscriminately attack rapidly dividing cells and damage both normal host tissues and cancer cells. Many chemotherapeutic drugs act at specific phases during the cell cycle and are termed cycle-specific agents. Agents that interfere with DNA synthesis are called S-phase specific, and those that interfere with microtubules to disrupt mitosis are called M-phase specific. DNA-alkylating drugs are considered cell-cycle nonspecific because they damage cells whether or not they are dividing, making these agents more effective against slow-growing and solid tumors (Table 53-1).

Neoadjuvant (induction) chemotherapy is administered prior to the start of definitive therapy, that is, before surgical resection or radiation treatment. Theoretically, it can shrink the tumor, making surgical extirpation easier, and decrease morbidity by
decreasing the extent of resection. Depending on the degree of response, the tumor may not shrink and may in fact grow larger, increasing surgical morbidity and potentially compromising the curability of the operation. Surgical margins may be difficult to assess if there has been dramatic shrinkage of the tumor.