Antineoplastic Agents

alkylating agent: bischloroethyl amine (nitrogen mustard) prodrug: requires metabolic activation in liver. Oral administration possible. less highly reactive than mechloroethamine prototype

alkylating agent: bischloroethyl amine (nitrogen mustard). Prototype. Administered IV

alkylating agent: nitrosourea. Has 2nd chloroethyl group.

alkylating agent: nitrosourea.

metabolized to alkylating agent and free radical. Used against hodgkin's disease as part of MOPP regimen. No cross resistance w. other antineoplastic agents. Risk of developing leukemia bcuz of mutagenicity

platinum coordinating complex. DNA cross-linking. May inhibit DNA biosynthesis , but cell cycle nonspecific. Useful in combo regimens. Adverse: nephrotoxicity, acoustic nerve dysfxn

platinum coordinating complex. DNA cross-linking. May inhibit DNA biosynthesis , but cell cycle nonspecific. Useful in combo regimens. Adverse: nephrotoxicity, acoustic nerve dysfxn

antimetabolite: pyrimidine antagonist. Metabolites inhibits thymidylate synthetase, and are incorporated into newly synthesized DNA and RNA

antimetabolite: purine antagonist. Fraudulent base incorporation, activated by conversion to NMPs, NTPs by hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Resistance if enyzme levels downregulated. Eliminated by xanthine oxidase. Active form of azothioprine.

antimetabolite: purine antagonist. Fraudulent base incorporation, activated by conversion to NMPs, NTPs by hypoxanthine-guanine phosphoribosyl transferase (HGPRT). Resistance if enyzme levels downregulated

antimetabolite: pyrimidine antagonist. Oral prodrug of fluorouracil, requires thymidine phosphorylase, higher expression and thus activation in tumor tissues. Used for colon cancer and refractory breast cancer

antimetabolite. Pyrimidine antagonist. After conversions -->araCTP is inhibitor of DNA synthesis, also incorporated into DNA causing mutations and breaks. Requires deoxycitidine kinase (lost in resistant cells). "chain blocking nucleotide analog"

antimetabolite. Folic acid analog. Inhibits dihydrofolate reductase, blocking synthesis of DNA, RNA. Accumulates in cell as a polyglutamate derivative (enhanced toxicity)

folinic acid rescue from methotrexate (source of tetrahydrofolate)

anti-tumor antibiotic. Or anthracycline. Highly potent, DNA intercalating. (-) DNA transcription via RNA polymerase. NOT cell cycle specific

anti-tumor antibiotic. Complex natural product, may cause anaphylaxis (small text doses to start). Mechanism for killing: DNA strand breakage. Effects broad spectrum of tumors. Risk of pulmonary fibrosis at large doses. No significant myelosuppression - used in ABVD

anthracycline anti-tumor antibiotic, topoisomerase inhibitor.

anthracycline anti-tumor antibiotic, topoisomerase inhibitor.

mitotic spindle poison. Plant alkaloid. Blocks microtubule Depolymerization. Used for ovarian and advanced breast cancers

mitotic spindle poison: vinca alkaloid. M-phase specific. Inhibits microtubule polymerization. SIDE EFFECTS: nausea, vomiting, bonemarrow depression (dose limiting). Used against lymphomas, Hodgkins. Part of ABVD. Resistance by tubulin gene mutations

mitotic spindle poison: vinca alkaloid. M-phase specific. Inhibits microtubule polymerization. SIDE EFFECTS: none acutely, milder (not dose limiting) bone marrow depression. significant neurotoxicity (muscle weakness). Used against acute childhood leukemia, lymphomas, Hodgkins. Part of M[O]PP. Resistance by tubulin gene mutations

topoisomerase inhibitor: camptothecin. Bind "cleaveable complex" of topo I and DNA, block religation of single-strand break. Use: colorectal cancer. Dose-limiting toxicity: diarrhea

topoisomerase inhibitor: camptothecin. Bind "cleaveable complex" of topo I and DNA, block religation of single-strand break. Uses: ovarian and lung cancers. Dose-limiting toxicity: myelosuppresion

topoisomerase inhibitor: topo II blocker. Forms ternary complex with it and DNA, interferes with religation.

adrenocorticosteroid. Suppresses mitosis of lymphocytes, used in combo regimens for leukemia, lymphoma, and myeloma. Palliative agent in other cancers (decrease swelling, pain)

antagonist of hormone action. SERM.

antagonist of hormone action. SERM. Approved for Tx of breast cancer. Lower associated risk of endo cancer and thrombotic events than tamoxifen.

antagonist of hormone action. SERM. Binds estrogen receptor, competes with estrogen. Partial agonist of receptor, efficacy varies on tissue. Adverse: hot flashes. Use: estrogen-responsive tissue cancers: breast (male and female) and uterine endometrium

antagonist of hormone action. Aromatase inhibitor, blocks conversion of androgens ot estrogen. Tx breast cancer

antagonist of hormone action. Aromatase inhibitor, blocks conversion of androgens ot estrogen. Tx breast cancer

antagonist of hormone action. Anti-androgen - analog of GnRH. Pulsatile delivery elevates levels of andro/estrogens. Continuous, high dose Tx lowers andro/estrogen. Chemical castration, ablation. Tx of prostatic cancer

antagonist of hormone action. Androgen receoptor antagonist. Ineffective alone due to rapid receptor mutation. Used w/ leuprolide to block initial pulse of high androgen levels and potential "flare" of prostate cancer when therapy starts

EGFR kinase inhibitor. Tx: non-small cell lung cancer

EGFR kinase inhibitor. Tx: non-small cell lung cancer

EGFR kinase inhibitor AND HER2 kinase inhibitor. In breast cancer trials

PDGFR, bcr/abl, kit(stem cell factor receptor) inhibitor. Tx: chronic myelogenous leukemia (bcr/abl mutation). GI stromal tumors (kit mutations), chronic myelomonocytic leukemia (ETV6-PDGFR fusion)

chimeric/humanized antibody, anti EGFR. Tx: colon cancer

chimeric/humanized antibody, anti CD20 (on Bcells) expressed in 90% of non-hodgkin's lymphomas. Ab binds and kills B cells effectively using complement and Ab dependent cell-mediated cytotoxicity

chimeric/humanized antibody, anti-HER2. "humanized" Tx for refractory metastatic breast cancer (HER2 elevated in 30% of breast tumors) Direct tumor cell, immune mediated effects.

alkylates w/ DNA. Cl- electrophiles search out neutrophiles. 2 branches w/ Cl- so can crosslink 2 bases.

hydrophobic, crosses BBB (useful against brain tumors). Little cross-resistancw with other alkylating agents. 1 chloroethyl group (2 in bischloroethyl amines)

mechloroethamine, vincristine (Oncovin), procarbazine, prednisone

drugs that target cells in S phase, inhibit metabolic actions needed in S-phase

amplification of DHFR gene, DHFR mutation, decreased uptake of methotrexate, increased efflux of methotrexate

intereferes w. purine metabolism to reduce uric acid accumulation associated with tumor cell death. Inhibits xanthine oxidase, which metabolizes 6-mercaptopurine)

DNA intercalation (put themselvesin the gap w/ anthracyclin ring). DNA topoisomerase II binding. NOT cell cycle specific. Irreversible cardiac toxicity at high doses. Severe or total alopecia at standard doses.

hair loss

combo regimen consisting of doxorubicin [A]driamycin] (anthracycline), bleomycin (antibiotic cuts DNA), vinblastine (microtubule poison), decarbazinel (alkylating agent)

selective estrogen response modulators

study of tamoxifen and raloxifene (as cancer preventitive agents)

arises from gene rearrangment/fusion in chronic myelogenous leukemia

alterations in drug uptake/transport. Increased concentration of target enzyme or decreased affinity of inhibitor for target enzyme. Decreased rate of metabolic drug activation. Increased rate of drug metabolism/inactivation. Increased rate of drug efflux.

nonspecific drug efflux pump