C

Chemotherapy

Description

Chemotherapy is the use of chemicals as a systemic therapy for cancer. It is a mainstay of cancer treatment for most solid tumors and hematologic malignancies (e.g., leukemias, lymphomas).The goal of chemotherapy is to eliminate or reduce the number of malignant cells present in the primary tumor and metastatic tumor site(s).

■ The two major categories of chemotherapeutic drugs are cell cycle phase–nonspecific and cell cycle phase–specific. These agents are often administered in combination to maximize effectiveness by using agents that function by differing mechanisms and throughout the cell cycle.

Classification of chemotherapeutic drugs

Chemotherapy drugs are generally classified according to their molecular structure and mechanisms of action (Table 92).

Table 92

Drug Therapy
Chemotherapy Drugs

Mechanisms of Action	Examples
Alkylating Agents
*Cell Cycle Phase–Nonspecific Agents*
Damage DNA by causing breaks in the double-stranded helix. If repair does not occur, cells will die immediately (cytocidal) or when they attempt to divide (cytostatic).	bendamustine (Treanda), busulfan (Myleran), chlorambucil (Leukeran), cyclophosphamide (Cytoxan, Neosar), dacarbazine (DTIC-Dome), ifosfamide (Ifex), mechlorethamine (Mustargen), melphalan (Alkeran), temozolomide (Temodar), thiotepa (Thioplex)
Nitrosoureas
*Cell Cycle Phase–Nonspecific Agents*
Like alkylating agents, break DNA helix, interfering with DNA replication. Cross blood-brain barrier.	carmustine (BiCNU, Gliadel), lomustine (CeeNU), streptozocin (Zanosar)
Platinum Drugs
*Cell Cycle Phase–Nonspecific Agents*
Bind to DNA and RNA, miscoding information and/or inhibiting DNA replication, and cells die.	carboplatin (Paraplatin), cisplatin (Platinol-AQ), oxaliplatin (Eloxatin)
Antimetabolites
*Cell Cycle Phase–Specific Agents*
Mimic naturally occurring substances, thus interfering with enzyme function or DNA synthesis. Primarily act during S phase. Purine and pyrimidine are building blocks of nucleic acids needed for DNA and RNA synthesis.
■ Interfere with purine metabolism	cladribine (Leustatin), clofarabine (Clolar), fludarabine (Fludara), mercaptopurine (Purinethol), nelarabine (Arranon), pentostatin (Nipent), thioguanine
■ Interfere with pyrimidine metabolism	capecitabine (Xeloda); cytarabine (ara-C [Cytosar-U, DepoCyt]), floxuridine (FUDR), 5-fluorouracil (5-FU [Adrucil]), gemcitabine (Gemzar)
■ Interfere with folic acid metabolism	methotrexate (Rheumatrex, Trexall), pemetrexed (Alimta)
■ Interferes with DNA synthesis	hydroxyurea (Hydrea, Droxia)
Antitumor Antibiotics
Cell Cycle Phase–Nonspecific Agents
Bind directly to DNA, thus inhibiting the synthesis of DNA and interfering with transcription of RNA.	bleomycin (Blenoxane), dactinomycin (Cosmegen), daunorubicin (Cerubidine, DaunoXome), doxorubicin (Adriamycin, Rubex, Doxil), epirubicin (Ellence), idarubicin (Idamycin), mitomycin (Mutamycin), mitoxantrone (Novantrone), plicamycin (Mithracin), valrubicin (Valstar)
Mitotic Inhibitors
Cell Cycle Phase–Specific Agents
Taxanes
Antimicrotubule agents that interfere with mitosis. Act during the late G₂ phase and mitosis to stabilize microtubules, thus inhibiting cell division.	albumin-bound paclitaxel (Abraxane), docetaxel (Taxotere), paclitaxel (Taxol)
Vinca Alkaloids
Act in M phase to inhibit mitosis.	vinblastine (Velban), vincristine (Oncovin), vinorelbine (Navelbine)
Others
Microtubular inhibitors.	estramustine (Emcyt), ixabepilone (Ixempra), eribulin (Halaven)
Topoisomerase Inhibitors
Cell Cycle Phase–Specific Agents
Inhibit topoisomerases (normal enzymes) that function to make reversible breaks and repairs in DNA that allow for flexibility of DNA in replication.	etoposide (VePesid), irinotecan (Camptosar), teniposide (Vumon), topotecan (Hycamtin)
Corticosteroids
Cell Cycle Phase–Nonspecific Agents
Disrupt the cell membrane and inhibit synthesis of protein. Decrease circulating lymphocytes, inhibit mitosis, depress immune system, increase sense of well-being.	cortisone (Cortone), dexamethasone (Decadron), hydrocortisone (Cortef), methylprednisolone (Medrol), prednisone
Hormone Therapy
Cell Cycle Phase–Nonspecific Agents
Antiestrogens
Selectively attach to estrogen receptors, causing down-regulation of them and inhibiting tumor growth. Also known as selective estrogen receptor modulators (SERMs).	fulvestrant (Faslodex), raloxifene (Evista), tamoxifen (Nolvadex), toremifene (Fareston)
Estrogens
Interfere with hormone receptors and proteins.	estradiol (Estrace), estramustine (Emcyt), estrogen (Menest)
Aromatase Inhibitors
Inhibit aromatase, an enzyme that converts adrenal androgen to estrogen.	anastrozole (Arimidex), exemestane (Aromasin), letrozole (Femara)
Miscellaneous
Enzyme derived from the yeast Erwinia used to deplete the supply of asparagine (amino acid) for leukemic cells that are dependent on an exogenous source of this amino acid. Inhibits protein synthesis.	Erwinia asparaginase, L-asparaginase (Elspar)
Causes changes in DNA in leukemia cells and leads to cell death.	arsenic trioxide (Trisenox)
Suppresses mitosis. Appears to alter DNA, RNA, and protein.	procarbazine (Matulane, Natulan)