Types and Classifications of Chemotherapy

Besides being classified as cell cycle specific or non-specific agents, cytotoxic drugs are also classified based on their biochemical structure and mechanism of action. Classifications of cytotoxic drugs include alkylating agents, nitrosoureas, antimetabolites, antitumor antibiotics, plant alkyloids, taxanes, hormonal agents, and miscellaneous agents.

Alkylating agents interfere with DNA replication to prevent cancer cells from reproducing. Most alkylating agents are cell cycle non-specific. Alkylating agents can produce major toxicities affecting the hematopoietic system (the blood producing system of the bone marrow), and the gastrointestinal, and reproductive systems. These drugs are active against chronic leukemia, non-Hodgkin’s lymphoma, Hodgkin’s lymphoma, multiple myeloma, and some cancers of the lung, breast, and ovary. The following cytotoxic drugs are examples of alkylating agents: busulfan, carboplatin, chlorambucil, cisplatin, cyclophosphamide, dacarbazine, ifosfamide, mechlorethamine hydrochloride, melphalan, procarbazine, thiotepa, and uracil mustard.

Nitrosoureas interfere with enzymes needed for DNA repair. The nitrosoureas are able to cross the blood-brain barrier, so they are used to treat brain tumors as well as non-Hodgkin’s lymphoma, multiple myeloma, and malignant melanoma. Most nitrosourea drugs are cell cycle nonspecific. Major toxicities occur in the hematopoietic and gastrointestinal systems. Carmustine, lumustine, and streptozocin are examples of nitrosoureas.

Antimetabolites interfere with DNA and RNA growth. Antimetabolites are used to treat chronic leukemias as well as tumors of the breast, ovary, and the gastrointestinal tract. Most antimetabolites are cell cycle specific and act in the S phase of the cell cycle. Major toxicities occur in the hematopoietic and gastrointestinal systems. Antimetabolites include drugs such as 5-fluorouracil, 6-mercaptopurine, capecitabine, cytosine arabinoside, floxuridine, fludarabine, gemcitabine, methotrexate, and thioguanine.

Antitumor antibiotics interfere with DNA by stopping enzymes needed for cell division or by altering the membranes that surround cells. These agents are cell cycle non-specific.Major toxicities affect the hematopoietic, gastrointestinal, reproductive, and cardiovascular systems. Antitumor antibiotics include dactinomycin, daunorubicin, doxorubicin, idarubicin, mitomycin-C, and Mitoxantrone.

Plant alkaloids inhibit or stop mitosis or inhibit enzymes that prevent cells from making proteins needed for cell growth. Most plant alkaloids are cell cycle specific, acting in the M phase. Major toxicities occur in the hematopoeitic, integumentary, neurologic, and reproductive systems. Frequently used plant alkaloids include vinblastine, vincristine, vindesine, and vinorelbine.

The taxanes include drugs such as paclitaxel and docetaxel. Taxanes have a unique way of preventing the growth of cancer cells – they affect cell structures called microtubules that play an important role in cell functions. In normal cell growth, microtubules are formed when a cell starts dividing. Once the cell stops dividing, the microtubules are broken down or destroyed. Taxanes stop the microtubules from breaking down and cancer cells become so clogged with microtubules that they cannot grow and divide. Paclitaxel is used for advanced ovarian cancer and as an initial treatment for ovarian cancer in combination with cisplatin. The FDA has also approved paclitaxel for the treatment of breast cancer that recurs within 6 months after chemotherapy or that has spread to nearby lymph nodes or other parts of the body. Paclitaxel is also used for other cancers, such as AIDS-related Kaposi’s sarcoma and lung cancer.

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Taxanes are used in the treatment of prostatic cancer.
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Hormonal agents and hormone-like drugs are used to treat some types of cancer, such as leukemia, lymphoma, and multiple myeloma. Hormones are often combined with other types of chemotherapy drugs to increase their effectiveness. Sex hormones are used to alter the action or production of female or male hormones and are used to slow the growth of breast, prostate, and endometrial cancers.

Tamoxifen is an example of a hormonal agent that interferes with the activity of estrogen. Estrogen promotes the growth of breast cancer cells. Tamoxifen, which is often referred to as an "anti-estrogen", works against the effects of estrogen on these cells. While tamoxifen acts against the effects of estrogen in breast tissue, it acts like estrogen in other tissues. Tamoxifen is used as adjuvant, or additional therapy following primary treatment for early state breast cancer. In women at high risk of developing breast cancer, tamoxifen reduces the chance of developing the disease. Tamoxifen is also used to treat men with breast cancer.

Miscellaneous agents include drugs such as bleomycin, hydroxyurea, L-asparaginase, and procarbazine.

Please visit the Clinical Trials site of the National Cancer Institute.

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What is the name of the new class of drugs that is showing some promise for treatment of breast cancer?

Chemoprotective agents are a new class of drugs that are designed to protect the body against specific toxic effects of chemotherapy. Dexrazoxane is a cardioprotective agent used with the antitumor antibiotic drug doxorubicin. Amifostine is a cytoprotective agent used to reduce potential renal toxicity associated with cumulative doses of cisplatin.
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Drugs in the nitrosourea class are used to treat brain cancer because they cross the blood brain barrier.
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