Understanding the Functions of Different Chemotherapy Agents

Chemotherapy is one of many treatment options for patients with cancer. This form of therapy uses chemical agents (i.e., anti-cancer or cytotoxic drugs) that interact with cancer cells to eradicate or control the growth of cancer. Common alternative forms of treatment include surgery to remove all or a portion of a tumor as well as radiation therapy, hormone therapy, and immunotherapy.

Understanding cancer
Although cell division is a normal part of the body’s growth, cancer occurs when cells divide uncontrollably. Normal cells divide through a cell cycle that includes an ordered set of events beginning with the synthesis of DNA (i.e., the S-phase) and mitosis (i.e., the M-phase). The cycle culminates in cell growth and division into two daughter cells. Normal cells also grow and die in a precisely controlled manner. Cancer occurs when the process becomes abnormal, meaning cells divide and form additional cells without control and order.

How chemotherapy works
The purpose of chemotherapy drugs is to interfere primarily with the synthesis of DNA to destroy the cells as they are formed. Different chemotherapy agents destroy cells using various methods. For example, some agents damage a cell’s genetic material. Others prevent the cell from dividing. Cancer cells that synthesize DNA and rapidly divide during mitosis are more vulnerable to the effects of chemotherapy than those in a resting place. A resting place (also known as G zero) refers to a state in which cells don’t divide and/or progress.

Since chemical agents damage cancer cells in different ways and at different phases in the cell cycle, providers often use a combination of drugs to increase the likelihood that all cancerous cells will be killed. Chemotherapy agents are administered in treatment cycles, either as a single agent or in a combination regimen. A combination regimen includes two or more chemotherapy agents with or without other systemic treatments.

Types of chemotherapy
Four types of chemotherapeutic agents exist. Each type is based on the mechanism of action (i.e., how the agent attacks the cancer cell) and at what point in the cell cycle the agent exerts these effects. Consider the following chemotherapy types:

1. Alkylating agents: These agents interfere with the cell function and replication. They are non-specific to the cell cycle and will kill cells in multiple phases of the cell cycle, including the rest phase for some. Although alkylating agents may be used for most types of cancer, they are generally most effective when treating slow-growing cancers. Alkylating agents are not as effective when treating rapidly growing cells.

2. Antimetabolites: These agents replace natural substances as building blocks in DNA molecules, thereby altering the function of enzymes required for cell metabolism and protein synthesis. In other words, they mimic nutrients that the cell needs to grow, thereby tricking the cell into consumption at which point the cell eventually starves to death. Antimetabolites are cell-cycle specific and exert their effects primarily during the S-phase.

3. Natural agents:

•Antitumor antibiotics are cell-cycle nonspecific. These agents act by binding with DNA and preventing RNA synthesis, a key step in the creation of proteins that are necessary for cell survival. Antitumor antibiotics are not synonymous with the antibiotics used to treat bacterial infections. Rather, these drugs cause the strands of genetic material that make up DNA to uncoil, thereby preventing the cell from reproducing.

•Plant alkaloids are antitumor agents derived from plants. These drugs block the ability of a cancer cell to divide and become two cells. Although these drugs act throughout the cell cycle, some are more effective during the S- and M- phases.

•Taxanes are plant products that prevent cancer cells from dividing. Taxotere, the most common taxane, inhibits the division of cancer cells by acting on the cell’s internal skeleton.

•Enzymes slow the growth of cancerous cells that cannot manufacture the enzyme L-asparagine. The enzymes don’t affect normal cells that can produce this enzyme properly.

4.  Miscellaneous:

•Platinum-based agents are cell-cycle specific and work by cross-linking DNA strands.

•Hydroxyurea inhibits enzyme production.

•Procarbazine splits DNA strands and causes chromosomal breaks.

Coding chemotherapy

Why is it important for cancer registrars to understand the different chemotherapy agents in order to code chemotherapy correctly?

When abstracting, code chemotherapy that is part of the first course of treatment. If the managing physician changes one of the agents in a combination regimen—and the replacement agent belongs to a different group than the original agent—the new regimen represents the start of subsequent therapy. Only the original agent or regimen is recorded as the first course of therapy.

Consider the following examples:

Scenario #1
Patient was given Cytarabine and then switched to Thioguanine.
Cytarabine is an antimetabolite. Thioguanine is also an antimetabolite.
Code as single agent, first course of treatment.

Scenario #2
Patient was given Cytarabine and then switched to Cyclophosphamide.
Cytarabine is an antimetabolite. Cysclophosphamide is an alkylating agent.
Code Cytarabine as single agent, first course of treatment. Do not code Cyclophosphamide because it is now part of the second course of treatment.

Scenario #3
Patient was given R-CHOP and then switched to COMP.
R: Rituxan is immunotherapy. Do not code under chemotherapy.
C: Cyclophosphamide is an alkylating agent.
H: Hydroxydaunorubicin (Doxorubicin) is an antitumor antibiotic.
O: Oncovin (Vincristine) is a plant alkaloid.
P: Prednisone is a hormone. Do not code under chemotherapy.

C: Cyclophosphamide is an alkylating agent.
O: Oncovin (Vincristine) is a plant alkaloid.
M: Methotrexate is an antimetabolite.
P: Prednisone is a hormone. Do not code under chemotherapy.

For this case, the Hydroxydaunorubicin (antitumor antibiotic) was replaced by Methotrexate (antimetabolite).

Code R-CHOP as multiple agents, first course of treatment. Code Rituxan under immunotherapy and Prednisone under hormone therapy.

Do not code COMP since this is now second course of treatment.

Understanding SEER*Rx
SEER*Rx, an interactive antineoplastic drugs database, was developed as a one-step lookup for coding oncology drug and regimen treatment categories in cancer registries. The information in this database is effective for cancer diagnoses made on January 1, 2005 and after.

The search function gives users two options: (1) to search by single agent and (2) to search by combination agents. Be sure to select the regimen tab when searching for combination agents and to determine what agents are included in the combination or regimen treatment. Registrars will be able to determine the type or group to which the agent belongs and identify single and multiple agents.

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