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Flashcards in cancer drugs Deck (35):

cell cycle specific drugs


Topoisomerase inhibitors

Microtubule poisons


cell cycle non specific drugs 

Alkylating agents

Antitumor antibiotics


alkylating agents (classic)









alkylating agetns (non classic)





  • alkylating agent 
  • Nitrogen mustard
  • IV only - subcutaneous cuases necrosis
    • Use arterial supply that goes to tumor
  • HL = min - very fast
  • Adverse effects
    • Acute - N/V
    • Delayed - decreased blood counts, moderate with most doses
  • Primary use: hodgkins lymphoma (part of MOPP)      



  • alk agent
  • Oral or IV
  • Nitrogen mustard pro-drug - activated by host metabolism
  • Used for many leukemias and lymphomas
  • AE
    • Acute - N/V
    • Delayed - bone marrow depression
    • Alopecia
    • Sterile hemorrhagic cyctitis - signiture effect
      • A metabolite of this drugs is excreted in urine and can damage kidney cells 



  • alk agent 
  • Analog of cyclophosphamide
  • IV only
    • It is also a pro-drug but it is not absorbed well
  • Used for Hodgkins and NHL
    • High does ofr bone marrow or stem cell rescue - can be used as ablation therapy
    • Component of ICE (ifosfamide, carboplatin, etoposide)
  • AE
    • Acute: N/V, urinary tract tox
    • More severe bone marrow depression than cyclophosphamide = leukopenia
    • Peripheral neuropathies
    • CNS effects
      • Hallucinations, coma
      • May be due to chloracetaldehyde - metabolite of the drug



  • alk agent 
  • Phenylalanine nitrogen mustard
  • Highly reactive, chemical half life - 50 min
  • Oral absorption inconsistent - primarily given IV
  • Renal excretion
  • Marked myelosuppression
  • Uses: multiple myeloma, myoablative therapy



  • alk agent 
  • Nitrogen mustard
  • Administered orally - once daily
  • Plasma half life - 1.5 hours
  • Was primary drug for CLL - now used only rarely



  • alk agent 
  • Alkylsulfonate
  • Oral, IV for high dose
  • Prior to imatinib, this was the key drug for CML
  • Profound myelosuppression; high dose produces pulmonary fibrosis, hepatic veno-occlusive disease



  • alk agent (non classic)
  • Nitrogen mustard
  • IV - HL - 30 min
  • Alkylates DNA but inhibits mitotic checkpoints - does two things
    • This makes it good for patients who are resistant to alkylating agents
  • Approved for CLL and indolent B cell NHL
  • Typical alkylating agent adverse effects: N/V, myelosuppresion and mucositis 



  • alk agent (non classic)
  • IV
  • Activated by hepatic metabolism
  • AE: severe N/V, delayed myelosuppresion (dose limiting)
  • Used to treat HL, multiple myeloma



  • alk agent (non classic)
  • Oral
  • Inhibits DNA, RNA, and protein synthesis; causes strand breaks
  • Higher potential for secondary malignancy than with other alkylating agents
  • Used for H/NHL




purine analogs (6-mercaptopurine, 6-thioguanine, fludarabine, cladribine)

pyrimidine analogs 




  • antimetabolite 
  • Dihydrofolate reductase substrate and inhibitor
  • Tumor cells are more sensitive than normal cells = Greater accumulation in tumor cells
  • Blocks production of bases for DNA synth
  • Orally, IV, intrahtecally (doesn’t cross BBB)
  • Excreted in urine
  • May give high dose - followed by rescue with folinic acid (citrovorin, leucovorin)
  • AE
    • Antifolate effects (bone marrow and GI problems)
    • Chronic use can produce hepatotox - usually this is in patients taking it chronically for RA
  • Resistance - decrased drug accumulation, amplified DHFR, altered DHFR


6-mercaptopurine, 6- thioguanine 

  • pruine analogs 
  • Oral
  • AE: Well tolerated - bone marrow depression at high doses
  • Blocks DNA and RNA synthesis - 6-MP inhibits AMP and GMP synthesis (stops the purine base synthesis), 6-TG incorperates into DNA or RNA and alters the function
  • Resistance from decrease in hprt activity or increase in alkaline phosphatase
    • Hprt - enzyme in the purine salvage pathway - don’t need to make as much if you can salvage it   



  • purine analog 
  • Orally or IV as monophosphate
  • Dephosphorylated in plasma and absorbed by cells -> Once it gets into cells its phosphorylated just like any other nucleotide
  • Diphosphate inhibits ribonucleotide reductase
  • Triphosphate inhibits DNA poly and ligase, can also get incorporated into RNA/DNA and cause problems with replication
  • Effective as mono- or combiantion for CLL
  • AE: myelosuppresion, N/V


Cladribine (2-chlorodeoxyadensosine - 2-CDA)

  • adenosine look alike (anitmetabolite)
  • IV
  • Activated by deoxycytidine kinase (host enzyme that puts the first phosphate on it)
  • Triphosphate incorporated into DNA - causes strand breaks
  • Inhibits ribonucleotide reductase
  • Used for hairy cell leukemia, CLL and low grade lymphomas
  • Resistance if deoxycytidine kinase activity is absent, if ribonucleotide reductase is upregulated or by active efflux
  • AE: bone marrow suppression is dose limiting


pyrimidine analog 

  • pyrimidine analog 
  • IV or intrathecal
  • Activated by deoxycytidine kinase - polymorphic
  • Triphosphate incorporated into DNA, inhibts elongation and repair
  • Used for therapy of AML, also ALL
  • Far more toxic than purines: myelosuppresion, GI disturbances stomatitis


plant alkyloids

microtuble poisionsin (vinca)

topoisomerase inhibitors (etoposide (VP-16))


vinca alkaloids

  • Basics
    • Biliary excretion
    • IV admin
    • Cuases metaphase arrest (CCS)
    • Inhibit/reverses tubulin polymerization, disrupts mitotic spindles (microtubles)
    • Isolated from vinca rosea (periwinkle)
    • microtubule poisons 
  • Drugs
    • Vinblastine
      • AE: N/V, alopecia, bone marrow depression
    • Vincristine
      • Structurally similar and mechanistically identical to vinblastine
      • Less toxic to bone marrow, no N/V
      • Use limited to short duration due to peripheral neuropathy - could be anything: numbness, pain, tingling in extremities


etoposide (VP-16)

  • Topo 2 inhibitor - double strand break (alows topo to break strands but not put back together), DNA degredation
  • Arrest cells in S-G2 stage (CCS)
  • Oral and IV
  • AE: N/V, alopecia, bone marrow suppression 


anti tumor antibiotics

anthracyclines (doxorubicin, daunorubicin, idarubicin)


  • Basics
    • Most produced by microbes (streptomyces)
    • Interact with DNA and/or RNA, but most do not alkylate - it is a non covalent interaction
    • These are still CCNS but they are more damaging if the cells are rapidly proliferating
    • Block access to/function of DNA or RNA
    • All given IV - these are large molecules and are not absorbed well
    • Unique toxicities associated with these compounds 



  • Doxorubicin, daunorubicin, idarubicin
    • Intercalate into DNA (slide inbetween the base pairs and cuase issues)
    • Block topoisomerase 2, inhibit DNA and RNA syntehsis, cuase strand breaks (allow the topo to break the strands - but doesn’t let them put it back together)
    • Generates free radicals
    • IV - metabolized in liver
    • AE: bone marrow suppresion, GI distress, severe alopecia
      • Signiture AE = cardiotoxicity
        • Function of cumulative dose
        • Idarubicin = less cardiotox
        • May be exacerbated by radiation or other drugs
          • You basically have to make a profile for the patient depending on: health status, age, other drugs - and then you can calculate a total lifetime dose that they can get without hurting the heart too bad
        • Arrhythmias, cardiomyopathy, CHF
          • These are selectively taken up in the mitochondria - have lots of this in heart muscle cells
        • Free radical mechanism
          • Minimize by administering dexrazoxane (this is not an anticancer drug - it binds iron and other things and prevents them from reacting with the reactive O2 species



  • Mixture of glycopeptides
  • Binds DNA, generates radicals
    • Cuase strand breaks
    • Active in G2 (CCS) - we don’t know why its CCS it just is
  • AE
    • Hypersensitivity and cutaneous reactions can happen
    • Pulmonary toxicity = fibrosis (signature tox)


targeted therapies 

hormones and hormone modulatiors

biologicals (asparaginase, rituximab)

singal transduction inhibitors (TK inhibtors - imatinib, dasatinib, ibrutinib, idealalisib)

protosome inhibitors (bartezimib)

differentiating agents (ATRA, arsenic trioxide, lenalidomide)



imatinib (gleevec)

  • Inhibits Bcr-ABL and c-KIT tyrosine kinases
    • These are unique kinases that are only expressed in cancers with philadelphia chrom - hits the cancer without hitting other cells
  • Blocks growth factor signaling in CML
  • Used in any hematologic malignancy with philadelphia chrom
  • AE: myelosuppresive
    • Mild AE: edema and fluid retention, hepatotoxicity - many times these do not manifest


dasatinib, nilotinib

  • Newer receptor tyrosine kinase inhbitors, broader spectrum
  • Useful when resistance to or poor tolerability to imatinib
    • The BCR-ABL gene can undergo mutation so that the protein produced wont bind to imatinib any more = resistance



  • Inhibits brutons tyrosine kinase (BTK)
    • Essential kinase for B cell receptor signaling 
  • Oral
  • Metabolized by CYP3A4 - metabolite is 15X more potent as BTK inhibitor
  • High activity agasint mantle cell lymphoma, relapsed/refractory CLL (expecially with 17p deletion)
  • AE: GI, thrombocytopenia, neutropenia, infections, fatigue
    • More cells in the body use BTK than for BCR-ABL (which no cells except the cancer cells use) - so the AE are worse 



  • Oral PI3K inhbiotr
  • Metabolized by aldehyde oxidase and CYP3A4 (strong CYP3A inhibitor = slow substrate)
  • Active agaisnt relapsed CLL and SLL, relapsed follicular B cell NHL
  • AE: potentially fatal hepatotox, diarrhea/colitis, pneumonitis, intestinal perforation 



  • Inhibits 26S proteosome
    • Disrupts multiple intracellular signaling cascades
    • Leads to apoptosis
  • IV
    • HL = 5.5 hr - HL of inhibiton = 24 hr (it stays in tissue for a while)
  • Used for mulitple myeloma, mantle cell lymphoma
  • AE: thrombocytopenia, fatigue, peripheral neuropathy - not in all patients
    • Hypotension upon infusion 


all trans retinoic acid (ATRA)

  • Used as mono therapy or with anthracycline or arsenic for APL
  • Binds to RAR-alpha receptor = promotes differentiation
  • Also promotes degradation of PML-RAR-a fusion protein, activates RAR-gamma
  • Resistance though enhanced clearance (CYP26A1 - not a CYP that we have heard about at this point in school) or loss of expression of fusion gene 


arsenic trioxide (As2O3)

  • Inhibits thioredoxin reductase - enhancing oxidative stress
  • Promotes modification and degradation of APL fusion protein
  • Cytotoxic and promotes differentiation



  • Thalidomide derivative
  • Used for CLL, mulitple myeloma
  • Lacks teratogenic, sedative effects of thalidomide
    • Thalidomide was used in UK as anti nausea meds for morning sickness - unfortunataly it was a teratogen and lots of babies were affected
  • May inhibit effects of rituximab - this drug downregulates the expression of CD20