Transfer alkyl groups to various cellular constituents.  Alkylations of DNA within the nucleus probably represent the major interactions that lead to cell death.

Occur in rapidly growing tissues – bone marrow, GI tract, reproductive system

Nausea and vomiting

Cancer

Transfer alkyl groups to various cellular constituents.Alkylations of DNA within the nucleus probably represent the major interactions that lead to cell death.

Occur in rapidly growing tissues – bone marrow, GI tract, reproductive system

Nausea and vomiting

Cancer

Transfer alkyl groups to various cellular constituents.Alkylations of DNA within the nucleus probably represent the major interactions that lead to cell death.

Occur in rapidly growing tissues – bone marrow, GI tract, reproductive system

Nausea and vomiting

Cancer

Folate analog that inhibits dihdrofolate reductase (DHFR), interfering with the synthesis of tetrahydrofolate (THF), which is a key one-carbon carrier for purine nucleotide synthesis.

Mucositis, myelosuppression with neutropenia and thrombocytopenia

Hepatic toxicity

Breast cancer, head and neck cancer, osteogenic sarcoma, primary central nervous system lymphoma, non-Hodgkin’s lymphoma, bladder cancer, choriocarcinoma

Inhibits purine nucleotide synthesis; incorporates triphosphate into RNA and DNA

Myelosuppression, immunosuppression, hepatotoxicity

Acute myelogenous leukemia (AML)

Inhibits thymidine synthase; incorporates 5-fluorouridine-5’-triphosphate (FUTP) into RNA resulting in alteration in RNA processing; incorporation of FdUTP into DNA resulting in inhibition of DNA synthesis

Mucositis, bone marrow depression, neurotoxicity

Colorectal cancer, anal cancer, breast cancer, gastroesophageal cancer, head and neck cancer hepatocellular cancer

Inhibition of tubulin polyermization, which disrupts assembly of microtubules. This results in mitotic arrest in metaphase leading to cell death.

Myelosuppression, mucositis, alopecia, SIADH, vascular events

Hodgkin’s and non-Hodgkins’ lymphoma, germ cell cancer, breast cancer, Kaposi’s sarcoma

Inhibition of tubulin polyermization, which disrupts assembly of microtubules. This results in mitotic arrest in metaphase leading to cell death.

Neurotoxicity with peripheral neuropathy, paralytic ileus, myelosuppression, alopecia, SIADH

Acute lymphoblastic anemia (ALL), Hodgkin’s and non-Hodgkin’s lymphoma, rhabdomyosarcoma, neuroblastoma, Wilms’ tumor

Acts as mitotic spindle poison by binding to microtubules and enhancing tubulin polymerization in the absence of microtubule-associated proteins and guanosine triphosphate.  Results in inhibition of mitosis and cell division.

Hypotension, arrhythmias, hypersensitivity, myelosuppression, peripheral sensory neuropathy

Breast, non-small cell and small cell lung, ovarian, prostate gastroesophageal, bladder, head and neck

Inhibits topoisomerase II, which results in

DNA damage through strand breakage induced by the formation of a ternary complex of drug, DNA, and enzyme

Hypotension, alopecia, myelosuppression

Non-small and small cell lung, non-Hodgkin’s lymphoma, gastric

Inhibit topoisomerase I, the key enzyme for cutting and re-ligating single DNA strands, resulting in DNA damage.

myelosuppression

Small cell lung, ovarian

Cytotoxic action through 4 mechanisms:

(1) Inhibits topoisomerase II

(2) Binds to DNA through intercalation, which blocks synthesis of DNA and RNA, and causes DNA strand scission

(3) Generation of free radicals

(4) Bind to cellular membranes to alter fluidity and ion transport

Red urine (not hematuria), alopecia, myelosuppression, stomatitis

Cardiac toxicity: (acute) arrhythmias, pericarditis, myocarditis; (chronic) cardiomyopathy and heart failure

Breast, Hodgkin’s and non-Hodgkin’s lymphoma, soft tissue sarcoma, ovarian, non-small and small cell lung, thyroid, Wilms’ tumor, neuroblastoma

Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks

Allergic reactions, fever, hypotension, skin toxicity, pulmonary fibrosis, mucositis, alopecia

Hodgkin’s and non-Hodgkin’s lymphoma, germ cell, head and neck

Acts as an alkylating agent and forms cross-links with DNA; formation of oxygen free radicals, which target DNA

Myelosuppression, mucositis, anorexia and fatigue, hemolytic-uremic syndrome

Superficial bladder, gastric, breast, non-small cell lung, head and neck

Androgen receptor antagonist

Mild gynecomastia, reversible hepatic toxicity

Prostate cancer

Selective estrogen receptor modulator (SERM); competitive partial agonist inhibitor of estradiol at the estrogen receptor

Estrogen receptor antagonist (breasts)

Estrogen receptor agonist (bones)

Hot flushes, nausea, vomiting

Palliative treatment of breast cancer in postmenopausal women and chemoprevention of breast cancer in high-risk women;

prevent osteoporosis

Glucocorticoid

Hypertension, fluid retention, diabetes, ↑susceptibility infection

Cataracts, fat redistribution, glaucoma, muscle wasting, peptic ulcers

Rx: control proliferation of

corticosteroid sensitive tumors

(Hodgkin's, non-Hodgkin's, etc.)

GnRH receptor agonist; suppresses FSH &

LH release in the long-term

Gynecomastia, hot flashes,

impotence

prostate

Selective nonsteroidal inhibitor of aromatase, the enzyme required for estrogen synthesis

Fatigue, hot flashes, arthralgias

Breast cancer