Combination Chemotherapy

Combination chemotherapy involves using two or more drugs proven effective against a tumor type. The development of this strategy has accounted for major advances in cancer treatment. Tumors in their early stages grow rapidly because they have a high growth fraction. Over a period of time, as the number of cancer cells grows and the tumor burden increases, the tumor’s growth fraction begins to decrease. Cell-cycle specific and cell-cycle non-specific drugs are given in combination, because the cell-cycle specific drugs reduce the tumor growth factor, and cell-cycle non-specific drugs help to reduce the tumor burden. Combination chemotherapy is given in courses or cycles. The number of courses varies, depending on the type of cancer, the cytotoxic drugs used, and the patient’s response to therapy. Combination therapy protocols are usually described by abbreviations that use the first letter of each drug in the protocol. For example, CAF (Cyclophosphamide + Adriamycin + Fluorouracil) is a combination protocol used to treat breast cancer.

There are several advantages of using a combination of drugs rather than a single agent.

a. Combining drugs that act in different phases of the cell cycle increases the number of cells exposed to cytotoxic effects.
b. Combining drugs decreases the incidence and severity of side effects of therapy.
c. Combinations of drugs are often effective in patients with large tumors containing a small number of cells that are reproducing. In this instance, one of the drugs kills a high proportion of tumor cells and stimulates the remaining tumor cells to start reproducing. The other drugs in the combination therapy can then attack newly reproducing cells.
d. Combining agents decreases the possibility of drug resistance.

Combinations of cytotoxic drugs can be given to achieve specific treatment goals. Adjuvant therapy refers to a short course of high-dose combination drugs given after radiation or surgery to destroy residual cancer cells.

Induction therapy involves giving a combination of high-dose drugs to create a complete response to therapy. Induction therapy is often used to treat bone marrow cancers. The term consolidation therapy refers to chemotherapy continued after induction therapy has produced a remission. Consolidation therapy is often repeated to increase the cure rate or to prolong survival. Maintenance therapy refers to using single drugs or combinations of drugs at low doses on a long term basis for patients who are in complete remission or to prevent the growth of residual or remaining cancer cells.

Factors influencing the response to cytotoxic agents include:

a. Tumor characteristics, such as location, size, growth rate, and presence of resistant cells
b. Availability of combination cytotoxic regimens for specific cancers
c. Hormone receptor status
d. Administration schedule and combinations of other forms of cancer therapy such as radiation therapy or surgery
e. Physical and psychosocial status of the patient