Chemotherapy treatment, risk, side effects and cancer

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 commonly the treatment of first choice for LEUKEMIA, lymphoma, MULTIPLE MYELOMA, metastatic cancers, inoperable cancers, and as adjuvant therapy following or accompanying another method, such as surgery, that is the primary treatment. Sometimes chemotherapy is an appropriate choice for palliative 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 symptoms and keep it from spreading.

How Chemotherapy Works to Treat Cancer

Chemotherapy drugs, also called chemotherapeutics or antineoplastic (“against new growth”) drugs, work by interfering with cell growth, activity, or division. Many of them directly damage DNA, the cell’s GENETIC CODE that directs the cell’s processes for growth and replication. Chemotherapy drugs are toxic to all cells in the body. However, 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 (intravenous, 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 effective against many types of cancer. Consequently many chemotherapy protocols include an alkylating agent. Some of the alkylating agents require METABOLISM by CYTOCHROME P450 (CYP450) ENZYMES, a large group of enzymes in the LIVER that metabolize many kinds of drugs, to be effective. Many factors, including genetic encoding and diet, affect the function and efficiency of CYP450 enzymes.

Antimetabolites

The antimetabolites derive from chemical structures similar to vitamins and amino acids (called metabolites) though are useless 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 treating leukemia, lymphoma, COLORECTAL CANCER, BREAST CANCER, BLADDER CANCER, PANCREATIC CANCER, and osteosarcoma. Antimetabolites have numerous side effects, including NAUSEA, HAIR loss, and tubular nephritis (damage to the KIDNEYS). Oncologists may give leucovorin along with the antimetabolite to counter these side effects.

Antibiotic chemotherapy agents

The anthracyclines and the related DRUG bleomycin are antibiotics that come from the FUNGUS Streptomyces verticillus, which naturally occurs in soils primarily in Japan though also can be cultivated. These chemotherapy drugs work by forming free radicals that disrupt the structure of cellular DNA. They are particularly effective against leukemia, lymphoma, and many types of CARCINOMA, notably breast cancer. Bleomycin is similar to the anthracyclines, derived also from the S. verticillus fungus, but a different chemical composition and action in cells. It is most effective in combination with other chemotherapy agents for treating lymphoma and TESTICULAR CANCER. The most significant SIDE EFFECT of the anthracyclines is damage to the HEART, and of bleomycin damage to the LUNGS, as a result of free radical activity.

Camptothecins, etoposide, and vinca alkaloids

The camptothecins block the function of topoisomerase, an enzyme cells need to synthesize DNA. Their original source was the bark of the Camptotheca acuminata tree native to China. Etoposide has the same action but comes from the bark of the mandrake tree. Vinca alkaloids derive from the leaves of the Vinca rosea plant, a type of periwinkle. The vinca alkaloids disrupt cell division. Like the alkylating agents, the camptothecins, etoposide, and vinca alkaloids are effective in treating a broad spectrum of cancers from leukemia and lymphoma to carcinomas and some sarcomas.

Taxanes

The taxanes come from the bark of the Taxus brevifolia-the Pacific yew tree. They work as chemotherapy agents by blocking the ability of cells to form the structures necessary to divide. They also appear to enhance a number of immune functions and are particularly effective in treating some types of metastatic breast cancer. Currently there are two taxanes, each of which is often more effective in combination with other chemotherapy agents than alone. As well, each taxane has specific side effects: docetaxel can cause severe EDEMA (fluid retention) and paclitaxel can cause MUSCLE pain. Both drugs can cause NEUROPATHY (dysfunction of the nerves) and severe depletion of neutrophils (NEUTROPENIA), white BLOOD cells (leukocytes) important for fighting INFECTION. Neutropenia raises the risk for infection.

Platinum compounds

Platinum compounds disrupt cellular DNA function as well as the ability of cells to synthesize DNA. These chemotherapy agents are particularly effective in treating LUNG CANCER, testicular cancer, and colorectal cancer. They can cause kidney damage and neuropathy.

Risks, Side Effects, and Complications of Chemotherapy

Because chemotherapy is a systemic treatment, it affects all cells in the body. Those most severely affected are those that grow and divide rapidly. Though cancer cells are at the head of that list, some healthy cells in the body also grow and divide rapidly. Among them are the cells of hair follicles (which produce hair), blood, and gastrointestinal tract, accounting for the most significant side effects of chemotherapy: hair loss, ANEMIA, increased susceptibility to infection, nausea, VOMITING, and DIARRHEA. However, the extent to which these side effects occur varies across the spectrum of chemotherapy drugs, and many people receiving chemotherapy do not experience them.

Medications and complementary remedies such as GINGER may help with chemotherapy-related nausea. ACUPUNCTURE also provides relief from nausea and other discomforts. Antinausea medications in the 5-HT3 receptor antagonist family (dolasetron, granisetron, ondansetron, and palonosetron) are especially effective. The longterm risks of chemotherapy include increased likelihood of developing another cancer, notably lymphoma or leukemia (especially acute myeloid leukemia with alkylating agents). Repeated chemotherapy, such as with chronic cancers or multiple recurrences, damages and may destroy the BONE MARROW.

HAIR LOSS DURING CHEMOTHERAPY

The cells of the HAIR follicles divide rapidly and thus are highly susceptible to the effects of chemotherapy. Because of this, people lose their hair after undergoing chemotherapy. However, because hair follicle cells are healthy and normal in their structure and function, most of them are able to resume growth and division-and hair production-when chemotherapy ends.

See also ANTIBIOTIC MEDICATIONS; CELL STRUCTURE AND FUNCTION; INVESTIGATIONAL DRUGS; LEUKOCYTE; PHARMACODYNAMICS; PHARMACOKINETICS; RADIATION THERAPY; SURGERY FOR CANCER.

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