Facts on File Encyclopedia of Health and Medicine

See alsoADENOMA; ADENOMA-TO-CARCINOMA TRAN-
SITION; BLASTOMA; SARCOMA; SKIN CANCER.

chemotherapy Treatment for cancer that uses
cytotoxic drugs (drugs that destroy cells) to kill
cancer cells. About half of people who have cancer
receive chemotherapy. Chemotherapy is com-
monly the treatment of first choice for LEUKEMIA,
lymphoma, MULTIPLE MYELOMA, metastatic cancers,
inoperable cancers, and as adjuvant therapy fol-
lowing or accompanying another method, such as
surgery, that is the primary treatment. Sometimes
chemotherapy is an appropriate choice for pallia-
tive treatment that shrinks cancer tumors to
relieve symptoms such as PAIN. The goal of
chemotherapy may be to eradicate the cancer or
to keep the cancer in check to eliminate its symp-
toms and keep it from spreading.

How Chemotherapy Works to Treat Cancer

Chemotherapy drugs, also called chemotherapeu-
tics or antineoplastic (“against new growth”)
drugs, work by interfering with cell growth, activ-
ity, or division. Many of them directly damage
DNA, the cell’s GENETIC CODEthat directs the cell’s
processes for growth and replication. Chemother-
apy drugs are toxic to all cells in the body. How-
ever, they have the most significant action on cells
that are rapidly dividing, such as cancer cells. Most
chemotherapy drugs have a NARROW THERAPEUTIC
INDEX(NTI); there is a fine margin between their
helpful and harmful actions. This narrow margin
often causes unpleasant but predictable side effects
that subside at the end of treatment.

Chemotherapy Agents

More than 600 chemotherapy drugs are currently
available to oncologists, who often combine them
in dozens of treatment protocols to treat various
types of cancer. Chemotherapy drugs may be
administered by MOUTH (oral), injection (intra-
venous, intramuscular, or subcutaneous), local
application (topical or via instilled solution such as
into the BLADDER), and intrathecal catheter (into
the spinal canal).
Alkylating agents The alkylating agents are the
oldest type of chemotherapy drugs and derive
from nitrogen mustards, the chemical family to
which poisonous mustard gas belongs. These

chemotherapy drugs interfere with at least four

stages of cell division, making them highly effec-

tive against many types of cancer. Consequently

many chemotherapy protocols include an alkylat-

ing agent. Some of the alkylating agents require

METABOLISMby CYTOCHROME P 450 (CYP 450 ) ENZYMES, a

large group of enzymes in the LIVERthat metabo-

lize many kinds of drugs, to be effective. Many

factors, including genetic encoding and diet, affect

the function and efficiency of CYP450 enzymes.

COMMON ALKYLATING AGENTS

busulfan carmustine

chlorambucil cyclophosphamide

dacarbazine iphosphamide

lomustine mechlorethamine

melphalan procarbazine

thiotepa

Antimetabolites The antimetabolites derive

from chemical structures similar to vitamins and

amino acids (called metabolites) though are use-

less to cells. The chemical similarity is so close,

however, that cells mistake antimetabolites for

substances they need to carry out their metabolic

processes. However, the antimetabolites cannot

complete those metabolic processes, interfering

with the ability of cells to synthesize (make)

nucleic acid, an essential component of DNA.

Without new DNA, cells cannot divide. Though

each antimetabolite agent has specific cancers

against which it is most effective, as a group the

antimetabolites are particularly effective in treat-

ing leukemia, lymphoma, COLORECTAL CANCER,

BREAST CANCER, BLADDER CANCER, PANCREATIC CANCER,

and osteosarcoma. Antimetabolites have numer-

ous side effects, including NAUSEA, HAIRloss, and

tubular nephritis (damage to the KIDNEYS). Oncolo-

gists may give leucovorin along with the

antimetabolite to counter these side effects.

COMMON ANTIMETABOLITES

6-mercaptopurine 6-thioguanine

arabinosylcytosine capecitabine

cladiribine cytarabine

dacarbazine fludarabine

fluorouracil (5-FU) gemcitabine

methotrexate

chemotherapy 375