Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
28 Cards in this Set
- Front
- Back
MTX, MTX + LV
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Methotrexate, prodrug activated by addition of glutamates.
Mechanism: Folic acid mimic that inhibits the enzyme dihydrofolate reductase (DHFR) Clinical Uses: IV or orally administered for breast, colorectal, lymphoma, etc. Very versatile. Used with reduced folates (leukovorin rescue) Tox: Mucositis, kidneys, liver. Resist: Reduced uptake is major resistance mechanism. |
|
hydroxyurea
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: Deoxynucleotide synthesis antagonist. Inhibits ribonucleotide reductase.
Clinical: Leukemias, head and neck cancers. Tox: Standard Resistance: Overexpression of the reductase. |
|
5FU, ftorafur, 5FdU, 5FU + LV
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: The fluoropyrimadines are pyrimidine synthesis antagonists. They modify thymidylate synthase, but can also cause DSB's by being incorporated into DNA.
Clinical: IV and oral for colorectal and breast cancer, usually in combo. Tox: Bone marrow suppression. Resist: Decreased activity of the enzymes needed to activate it. |
|
6-thiopurine, 6-thioguanine, azathioprine
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: Purine biosynthesis antagonists. After activation, both act as inhibitors of enzymes in purine synthesis and are incorporated into DNA.
Clinical: Oral for leukemias. Tox: Bone marrow suppression. Resist: Inactivated by xanthine oxidase. |
|
Gemticitabine, cytarabine (Ara-C), fludarabine, 5-aza-C), cladribine
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: All inhibitors of DNA Polymerase. Activated by enzymes and then block DNA strand elongation after being incorporated.
Clinical: Gemcitabine for pancreatic, Cytarabine for AML, Fludarabine for chronic lymphocytic leukemia. Tox: Myelosuppression. Resist: Decreased activity of activating enzymes and nucleoside transport across CM. |
|
Gleevec (imatinib)
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism:Inhibits the autophosphorylation of three tyrosine protein kinases incl. BCR-ABL implicated in CML.
Clinical: CML, GI stromal tumors. Toxicity: Standard. Resistance: Amplification of the oncogenic PK gene. |
|
Herceptin (trastuzumab)
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: A humanized MAb binds to the extracellular TK region of HER2 from the EGFR family.
Clinical: 25% of breast cancers exhibit HER2 overexpression. Resist: Amplification of PK gene. |
|
Cetuximab
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: An anti-EGFR MAb.
Clinical: Epithelial tumors including colorectal cancer and head-and-neck tumors. Resist: Amplification of PK gene. |
|
Gefitinib
Mechanism Clinical uses Major toxicities Major resistance mechanisms |
Mechanism: Inhibitor of an EGFR TK.
Clinical: Non-small cell lung cancer (NSCLC). Resist: Amplification of PK gene. |
|
Neovastat, Gleevec, endostatin, angiostatin, fumagillin
Mechanism |
Mechanism: Anti-angiogenesis drugs that either block breakdown of the extracellular matrix or inhibit endothelial cell proliferation (ex: Gleevec).
|
|
Velcade
Mechanism Clinical use |
Mechanism: Proteasome inhibitor. Targets the chymotrypsin-like active site of the proteasome so the proteasome binds to the drug instead of protein and gets stuck.
Clinical: Upregulation of the transcription factor NF-kB in myeloma cells. Velcade binds to the proteasome that degrades NF-kB's inhibitor, thereby blocking transcription of NF-kB. |
|
mechlorethamine
Mechanism Clinical Use Toxicities |
Mechanism: Alkylating agent
Clinical: Used as part of MOPP (with Oncovin, Procarbazine, Prednisone) for Hodgkin's disease. Tox: Nausea, emesis, phlebitis, bone marrow suppression |
|
melphalan and chlorambucil
Mechanism Clinical Use Toxicities |
Mech: "Substituted" nitrogen mustard alkylating agents.
Clinical: B/c less reactive than mechlorethamine can be given orally for multiple myeloma (melph) or CLL (chlorambucil). Toxicities: Bone marrow, amenorrhea, sterility |
|
cyclophosphamide and ifosfamide
Mechanism Clinical Use Toxicities |
Mechanism: Modified nitrogen mustard alkylating agents.
Clinical: Require metabolic activation so given orally for many cancers including non-Hodgkins lymphoma as part of CHOP and breast cancer as part of AC. Ifosfamide is given for sarcomas and others. Tox: B/c of bone-marrow toxicity often given with marrow transplants. Also hemorrhagic cystitis--bleeding bladder. Early bone marrow stem cells are protected. |
|
carmustine, lomustine, semustine, streptozotocin
Mechanism Clinical Use Toxicities |
Mech: nitrosoureas.
Carmustine is used for brain tumors, has marrow, emesis, and nausea toxicities. Streptozotocin is an antibiotic retained in B-cells of islets of Langerhans and used for those tumors, with normal toxicities plus DM and nephro- and hepatotoxicity. |
|
thiotepa, mitomycin C
Mechanism Clinical Use Toxicities |
Mechanism: Aziridines/
Thiotepa is used for breast cancer and superficial bladder cancer, and has normal toxicities. Mitomcin C is an antibiotic for rectal and pancreatic cancer and has normal toxicities plus diarrhea and stomatitis, and rarely hemolytic-uremic syndrome (HUS). |
|
busulfan
Mechanism Clinical Use Toxicities |
Mechanism: Alkane sulfonate.
Clinical: Used as part of hgih dose chem preparative regimen for bone marrow or peripheral stem cell transplantation. Toxic: Bone marrow suppression, pulmonary fibrosis, skin pigmentation |
|
procarbazine and dacarbazine
Mechanism Clinical Use Toxicities |
Mechanism: Methylating agents.
Procarbazine is used for Hodgkin's as part of MOPP and has normal toxicities plus peripheral neuropathy and secondary leukemia. Dacarbazine is used for Hodgkin's as part of ABVD and has normal toxicities plus photosensitivity and Budd-Chiari syndrome. |
|
cisplatin, carboplatin, oxaliplatin
Mechanism Clinical Use Toxicities Resistance |
Mechanism: Platinum compounds likely target N-7 groups on guanine and adenine, leading to crosslinking of bases to the same or opposite strand or to proteins, RNA, or other macromolecules.
Clinical: Cisplatin and carboplatin are used for many cancers, especially epithelial and testis. Toxic: Cisplatin has nephrotoxicity, ototoxicity, and peripheral neuropathy, while carboplatin and oxaliplatin have standard toxicities. Resist: Chemical detoxification, DNA repair. |
|
Rituximab
Mechanism Clinical uses Resistance Toxicities |
Mech: Directly induces apoptosis by binding CD20 receptor on lymphocytes, marks tumor cells for killing by NK cells, fixes complement leading to cell lysis.
Clinical: Complete remission or reduction of B-cell lymphomas. Resistance: Rare! Failure to activate AB-dependent cytotoxicity, variations in apoptotic pathways. Toxicities: Inhibits new Ig responses, may increase susceptibility to infeciton. |
|
Antibody conjugates
Mechanism |
Radioimmunoconjugates or immunotoxins target CD20 and exhibit "crossfire", as neighboring cells are killed even if they aren't hit.
|
|
Topotecan and irinotecan (CPT-11)
Mechanism Clinical Use Toxicities |
Derivatives of camptothecin.
Mech: Topoisomerase I -targeted. Intercalation mechanism stabilizes complex. Irinotecan is a prodrug that must be activated. Clinical: Solid tumors including colorectal, ovarian, lung, etc. Tox: Normal, plus irinotecan causes liver toxicity in some patients and diarrhea. |
|
Minor Groove DNA-Binding Drugs
Mechanism |
Mech: Topoisomerase I-targeted. Maybe stabilize complex by DNA bending?
|
|
Actinomycin D
Mechanism Clinical Use Toxicities |
Mech: Topoisomerase I -targeted. Increases amount of covalent complex by inducing DNA bending, though maybe for RNA polymerase I instead of topo I.
Clinical: CHILDHOOD malignancies. Tox: Usual suspects. |
|
Etoposide and Teniposide
Mechanism Clinical Use Toxicities |
Epipodophylotoxins.
Mech: Topoisomerase II -targeted. Non-intercalative stabilizers of topo II complex. Clinical: Many cancers. Tox: Normal + anaphylaxis. |
|
Doxorubicin and Daunorubicin
Mechanism Clinical Use Toxicities |
Anthracyclines.
Mech: Intercalative, direct or indirect stabilizers of Topo II. Clinical: Doxo for solid tumors, Dauno for acute leukemias. Tox: Metabolism and toxicity occurs in the liver--free radicals produced! Also LOTS of cardiotoxicity. |
|
Vincristine, Vinblastine and Vinorelbine
Mechanism Clinical Use Toxicities |
Mitotic spindle poisons. Vinca alkaloids.
Mech: Slow microtubule polymerization dynamics. Clinical: Vincristine for blood, blastine for germ cell, orelbine for lung and breast. Tox: Significant liver, significant neuro (b/c axons have microtubules). |
|
Paclitaxel and docetaxel
Mechanism Clinical Use Toxicities |
Mitotic spindle poisons. Taxanes.
Mech: Bind to B tubulin and stabilize lateral tubulin contacts. Clinical: Pac for ovarian and breast, doce for breast. Tox: Normal, myelosuppression, and peripheral neuropathy (spindles!). |