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99 Cards in this Set
- Front
- Back
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5-Fluorouracil
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Uracil analog that inhibits thymidylate synthase to prevent THYMINE synthesis, S cycle specific, DLT-Myelo, also causes tear duct stenosis (epiphora)
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6-Mercaptopurine
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Converted by hypoxanthine guanine phosphoribosyl transferase to 6MP nucleotide that inhibits DNA/RNA formation, S cycle specific, DLT-Myelo
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Anastrozole
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Aromatase inhibitor (blocks conversion of androstenedione to estrone), few S/Es
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Bicalutamide
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Androgen receptor antagonist, S/E=gynecomastia, hot flashes, impotence, diarrhea
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Bleomycin
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Intercalates (inserts in) DNA causing strand breaks c Oxygen free radicals, G2 phase specific, DLT-***Pulmonary Fibrosis (do NOT forget this one)
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Busulfan
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Alkylating agent, not cycle specific, DLT-Myelosup.
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Capecitabine
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Converted intracellularly to 5-FU by thymidine phosphorylase (but administered PO!), S cycle specific, Derm toxicity (hand-foot Synd) (p 198 lists the derm S/E of this drug, but tear duct one for 5-FU... Go figure)
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Carboplatin
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Platinum Alkylating agent, not cycle specific, DLT-**Myelosup.
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Carmustine
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(BCNU) IV Nitrosurea Alkylating agent, not cycle specific, DLT-Myelosup.
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Cisplatin
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Platinum Alkylating agent, not cycle specific, DLT-***Nephrotoxicity (can mitigate by hydration c NS a & p infusion)
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Cyclophosphamide
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Alkylating agent, not cycle specific, DLT-Myelosup. (but platelets relatively spared), ***also toxic to bladder (hemorrhagic cystitis, etc)
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Cytarabine
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Phosphorylated inhibitor of DNA polymerase, S cycle specific, central CNS toxicity
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Doxorubicin
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Anthracycline (topoisomerase II inhibitor), not cycle specific, DLT-Myelo but also CARDIOTOXIC! Must keep total dose <550mg/m²
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Estramustine
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Inhibits microtubule assembly, M phase specific, DLT-Myelo
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Etoposide
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Topoisomerase II inhibitor (causes double stranded breaks in DNA), G2 phase specific, DLT-Myelo
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Imatinib
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Inhibits ATP binding to Bcr-Abl tyrosine kinase (product of t9:22 philly chromosome in CML), ? Cycle specific, no specific tox
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Irinotecan
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Topoisomerase I inhibitor (single stranded DNA breaks), G2 phase specific, DLT-delayed diarrhea ~ 24h p infusion
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L-asparaginase
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Causes hydrolysis of serum asparagine (essential amino acid for leukemia cells), G1 cycle specific, DLT-Hepatotoxicity (decreased K dependent clotting factors & albumin)
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Leucovorin
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BM rescue in Methotrexate usage
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Leuprolide
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GnRH agonist (overstimulation of receptors causes downregulation, thus decreases FSH/LH by 90% in 2 weeks), S/E=hot flashes, impotence, tumor flare up (can prevent tumor flare c bicalutamide)
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Levamisole
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Potentiates action of 5-FU
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Lomustine
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(CCNU) PO Nitrosurea Alkylating agent, not cycle specific, DLT-Myelosup.
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Methotrexate
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Binds Dihydrofolate Reductase (DHFR) so no makie purines/pyrimidines, S cycle specific, DLT-Myelo (prolonged c effusions) - BM rescue c leucovorin
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Oxaliplatin
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Platinum Alkylating agent, not cycle specific, DLT-***Neurotoxicity
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Paclitaxel
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Promotes microtubule assembly & *stabilizes against depolymerization, M phase specific, DLT-Myelo but also peripheral neurotoxic ~vincristine
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Procarbazine
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Alkylating agent, not cycle specific, DLT-Myelosup.
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Raloxifene
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Estrogen receptor antagonist, can cause hot flashes, fluid retention, poss endometrial CA
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Semustine
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(CCNU/Methyl) PO Nitrosurea Alkylating agent, not cycle specific, DLT-Myelosup.
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Tamoxifen
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Estrogen receptor antagonist, can cause hot flashes, fluid retention, poss endometrial CA
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Temozolamide
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Alkylating agent, not cycle specific, DLT-Myelosup.
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Teniposide
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Topoisomerase II inhibitor (causes double stranded breaks in DNA), G2 phase specific, DLT-Myelo
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Thalidomide
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Inhibits TNF-alpha preventing angiogenesis necessary for tumor blood supply, S/E=TERATOGENIC(phocomelia=no limbs), drowsiness, peripheral neuropathy, constipation
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Thiotepa
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Alkylating agent, not cycle specific, DLT-Myelosup.
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Topotecan
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Topoisomerase I inhibitor (single stranded DNA breaks), G2 phase specific, DLT-Myelo
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Trastuzumab
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Binds epidermal growth factor receptor (Her 2/neu), S/E=chills, fever during 1st infusion.***Also cardiotoxic!
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Vinblastine
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Vinca alkaloid inhibits microtubule assembly, M phase specific, DLT-Myelo (WBCs>platelets), also a vesicant (Tx c heat & intradermal hyaluronidase)
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Vincristine
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Vinca alkaloid inhibits microtubule assembly, M phase specific, Non-myelosuppressive! DLT-Neurotoxicity (Paresthesias, los of DTRs & GI motility), also a vesicant (Tx c heat & intradermal hyaluronidase)
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cyclophosphamide
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"p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) ~ cyclophosphamide produces (non)hemorrhagic cystitis (prevent with MESNA--free radicle scavenger, binds the acrolein metabolite of cyclo.) ~ busulfan, melphalan, chlorambucil, nitrosoureas - assoc. w/ pulmonary fibrosis, adrenal insufficiency
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5-fluorouracil
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"i.v., S, pyrimidine antimetabolite, 5-FU-PPP incorp. into RNA & F-dUMP inhibits thymidylate syn., blocks DNA synthesis, myelosuppression w/bolus, stomatitis, mucositis ""hand-foot syndrome"", painful desquamation of palms, soles
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6-mercaptopurine (6-MP)
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"p.o., S, Purine antimet., converted by hypoxanthine guanine phosphoribosyl transferase to 6MP or 6TG nucleotide, Inhibit purine synthesis
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6-thioguanine (6-TG)
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"p.o., S, Purine antimet., converted by hypoxanthine guanine phosphoribosyl transferase to 6MP or 6TG nucleotide, Inhibit purine synthesis
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a few words about MYELOSUPPRESSION (MSP) -
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the most common dose limiting toxicity- causes pancytopenia (anemia, thrombocytopenia, leukopenia) & assoc. sx's (infxn, fatigue, etc) - most cause MSP in a predictable manner, but some (carmustine, lomustine) have a nonpredictable biphasic MSP...delayed recovery Drugs that are cell cycle specific cause time dependent killing & drugs that are cell cycle nonspecific cause dose dependent killing
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anastrozole
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, , aromatase inhibitor, blocks conversion of androstenedione to estrone, , ,
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azaxitidine
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, S, pyrimidine antimetabolite, Methylation of DNA turns off tumor supressor gene; incorporation into mRNA, Inhibits the DNA methyltransferase and thus turns off tumor suppressor genes, myelosuppression,
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bicalutamide
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, , androgen antagonist, inhibits DHT binding, , gynecomastia, hot flashes, impotence, low libido,
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bleomycin
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", G2, Antitumor Antibiotics, intercalates (fragmentation of) DNA w/ O2 free radicals; cell accumul.; DNA synth stops, causes strand (""scission"") breaks, pulmonary fibrosis (""bleo blasts the lung"")
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bortezomib
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i.v., , Misc, Bortezomib prevents degredation of IkB by inhibiting activity of Proteasome 26S--enhancing apoptosis. (Proteasome 26S causes proteolysis of inhibitor (IkB) of NF-kB; NF-kB upregulates DNA transcr., cell survival, and inhibits apoptosis.), Used to treat multiple myeloma, ,
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Breast CA
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CMF, cyclophosphamide, methotrexate, 5-FU, , , , ,
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Breast CA
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CAF, cyclophosphamide, adriamycin = doxorubicin, 5-FU, , , , ,
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busulfan
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p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) ,
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capecitibine
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p.o., S, pyrimidine antimetabolite, metabolized to 5-FU, , ,
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carboplatin
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i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, DLT- myelosuppression; M RT, platinum agents; carboplatin has less GI tox.than cisplatin; all have high freq hearing loss and neurotox
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carmustine (BCNU)
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i.v., NS, G0, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , nitrosoureas hard to kill cells in G0; kill CNS tumors--cross BBB, require bioactivation - cause delayed & cumulative myelosuppression (see below)
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cetuximab
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, , monoclonal ab, Blocks the HER1 EGFR , Colon CA 60-75% express epidermal growth factor HER1 (ErbB1) which causes cell profliferation, survival, angiogenesis, ,
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chlorambucil
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p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) ,
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cisplatin
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i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, DLT- nephrotoxic, platinum agents; carboplatin has less GI tox.than cisplatin; all have high freq hearing loss and neurotox
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cytarabine (Ara-C)
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"sc/iv, S, pyrimidine antimetabolite, PO4-ylated inhibitor of DNA pol., Induction and relapse of AML, reversible cerebellar toxicity
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dactinomycin
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i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , antibiotics
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dactinomycin
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, NS, Antitumor Antibiotics, Intercalates into ds DNA b/w guanine-cytosine paris; DNA rep affected little, DNA-dep RNA synth impaird so protein synth blocked, , Myelo-/immuno suppression; radiation recall, skin irritation at prior irradiated site,
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darbepoetin
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, , antineoplastic, , , , Longer half life than eop
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doxorubicin
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", NS, Antitumor Antibiotics, 1) inhibits topoisomerase 2 (DNA scission, cell dies in G2)
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epoetin alfa
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", , antineoplastic, , fatigue, shortness of breath, Myelosuppression is the most common dose limiting toxicity
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estramustine
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, M, , , , ,
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etoposide
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, S-G2, Epipodophylotoxins, targets topoisomerase 2, maintains transient cleavable complex; stabilize bonds b/w topo II and DNA; Topo II inhibited so dsDNA breaks remain; DNA degrades, causes double strand breaks, dose-limiting myelosupression, anaphylaxis, fever, hypo- and hypertension, secondary leukemias, Topos cut single- double stranded DNA to allow strands to unwind; topo I (single strand) and II (ds) needed for DNA replic. And RNA transcrip; topo II needed for completion of mitosis
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filgrastim
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, , antineoplastic, granulocyte CSF, , , Give to treat infxn, fever (N0 below 1000)
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Fludarabine
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, , antineoplastic, Triphosphate of fludarabine, created by deoxycytidine kinase, inhibits DNA polymerase and ribonucleotide reductase., , ,
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gemcitabine
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i.v., S, pyrimidine antimetabolite, Added of gem tri-P to growing DNA strand results in chain termination, di- and triphosphates inhibit ribonucleotide reductase--thus deplete cell of deoxyribonucleoside TP needed for DNA synthesis, myelosuppression,
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Hodgkins (B cell CA)
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MOPP, mechlorethamine, oncovin = vinvristine, procarbazine, and prednisone, , , , ,
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Hodgkins (B cell CA)
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ABVD, adriamycin = doxorubicin, bleomycin, vinblastine, and dacarbazien, , , , ,
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hydroxyurea
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p.o., S, Misc, inhibits ribonucleotide reductase; Depletion of deoxynuc TP prevents DNA synthesis, Used to treat sickle cell; turns on HbF gene; HbF presence prevents sickling, Myelosuppression,
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imatinib
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, , enzyme inhibitors, blocks ATP binding to Bcr-Abl tyrosine kinase, , N/V, diarrrhea, edema, specific for CML Philadelphia chromosome (9,22)
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L-asparaginase
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i.v., G1, enzyme inhibitors, hydrolysis of serum asparagine, deprives neoplastic cells (esp. leukemias) of asparagine; normal cells can synth l-asp., hepatic toxicity,
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leucovorin
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, , antimetabolites, antidote for methotrexate (rescues normal cells from myelosuppression) - cancer cells can't take up leucovorin; BM rescue, aka folinic acid, , ,
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leuprolide
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, , GnRH agonist, stimulates FSH, LH release, reduces androgen, estrogen synthesis, hot flashes, impotence, ch
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levamisole
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, , immuno-modulator, potentiates 5-FU in pts w/ colon CA, Restores depressed immune fn in B, T, Mono, M0 cells, ,
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lomustine (CCNU)
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p.o., NS, G0, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , nitrosoureas hard to kill cells in G0; kill CNS tumors--cross BBB, require bioactivation - cause delayed & cumulative myelosuppression (see below)
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mechlorethamine
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"i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) ~ cyclophosphamide produces (non)hemorrhagic cystitis (prevent with MESNA--free radicle scavenger, binds the acrolein metabolite of cyclo.) ~ busulfan, melphalan, chlorambucil, nitrosoureas - assoc. w/ pulmonary fibrosis, adrenal insufficiency
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melphalan
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p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , Can cause secondary leukemias
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Mensa:
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Na-2-mercaptoethane sulfate, , , , , ,
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methotrexate
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"p.o., S, antimetabolites, folic acid analog- reversibly binds DHF reductase (in all cells) & prevents synthesis of reduced folates, purines, thymidylate, and AA serine and methionine. , can't make purines or pyrimidines…so can't make proteins, myelosuppression - GI toxicity (mucositis, hemorrhagic enteritis), also renal, hepatic, lung, neuro
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mitomycin-C
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i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , antibiotics
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mitomycin-C
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, NS, Antitumor Antibiotics, Alkylation cross-links DNA, esp. in hypoxic tumor cells, , severe myelosuppression,
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Non-Hodgek lymph
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CHOP, cyclophosphamide, doxorubicin (hydroxydaunorubicin), Oncovin = vincristine and prednisone, , , , ,
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oprelvekin (IL-11)
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, , antineoplastic, a megakaryocytge growth factor), Treat thrombocytopenia, , Recombo thrombopoetin in trials
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paclitaxel
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, M, Taxanes, promotes tubulin polym., assembly of microtubules & stabilizes them against disassembly; mitotic arrest as anaphase cannot occur; removes remodeling, also P-lates BCL-2 (antiapoptosis), Myelosuppression; peripheral neuropathy; myalgias; pretreatment with corticosteroids decreases severity of many other adverse effects (see notes), first-line agent for breast CA peripheral nerve toxicity
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pemetrexed
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, S, antimetabolites, inhibits DHF reductase & thymidylate synthase= multitarget antifolate, blocks DNA synthesis, myelosuppression, N/V, rash, renal clearance, so avoid NSAIDs
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Pentostatin
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i.v., S, Purine antimet., Irreversible inhibitor of adenosine deaminase, , Myelosuppression and immunosuppression,
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procarbazine
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p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , CNS depression
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raloxifene
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, , estrogen antagonist, blocks growth-promoting effects of estrogen , inhibits estrogen-dependent breast CA, hot flashes, N/V, vaginal discharge, not effective in pre-menopausal women
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rituximab
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, , monoclonal ab, Binds CD30 Ag expressed on all malignant B lymphomas, , ,
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sargramostim
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, , antineoplastic, granulocyte-macrophage CSF, , ,
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tamoxifen
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, , estrogen antagonist, , , ,
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temozolamide
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p.o., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , crosses BBB; does not need bioactivation; treats primary and secondary brain tumors
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thalidomide
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, , immuno-modulator, inhibits TNF-α, antiangiogenesis (inhibits new blood vessels), birth defects (phocomelia),
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thiotepa
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i.v., NS, alkylating agents, alkylates DNA (primarily at the N7 position of guanine & also at the O6 of guanine) ~ carmustine, lomustine, semustine & temozolamide alkylate DNA at O6 position, cytotoxic effects via cross-linking (two sites - bifunctional) & single strand breaks (one site - monofunctional) ↓ 1) inhibition of DNA, RNA & protein synth. 2) misreading of DNA, ALL CAUSE MYELOSUPPRESSION & IMMUNOSUPPRESSION (Dose limiting toxicity) , has special applications (intrathecal, intracavitary, intravesical, intraperitoneal) ex. pulm. effusion (lung CA)
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topotecan
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, NS, Capttothesins, inhibits topoisomerase 1 by stabilizing cleavable complex (cell can't repair DNA), causes single strand breaks & apoptosis, myelosuppression, diarrhea, diarrhea
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trastuzumab
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i.v., , monoclonal ab, binds to epidermal growth factor receptor (Her2/neu), inhibits Her2 cell proliferation, congestive heart failure, Helpful with cardiac dysfn, esp with doxorubicin
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vinblastine
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", M, Vinca Alkaloids, ""Spindle poisons"" prevent assembly (polymerization) of microtubules (late G2-early M);cell arrests late G2 b/c mitotic filaments cannot form (BJE--M phase); prevents the dynamic and constant remodeling
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vincristine
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", M, Vinca Alkaloids, ""Spindle poisons"" prevent assembly (polymerization) of microtubules (late G2-early M);cell arrests late G2 b/c mitotic filaments cannot form (BJE--M phase); prevents the dynamic and constant remodeling
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