antineoplastics Flashcards
what are the 3 dosing regimens
induction, consolidation, and maintenace
describe induction therapy
high does combination therapy
describe consolidation therapy
repetition induction during remission
describe maintenance therapy
long term, low dose therapy during remission
define neo-adjuvant
before or during surgery/radiotherapy
define adjuvant
after surgery/rediotherapy
what are the advantages of combination therapy
increases maximum cell kill, kills heterogeneous cell populations, decreased tumor resistance
define metronomic dosing
the use of lower doses more frequently (ie everyday)
define hormesis
the concept that drugs have different effects at different concentrations. therefore a drug that kills cells at high concentration may drive proliferation at low concentrations
how does metronomic dosing take advantage of hormesis
by dosing frequently, drug serum concentrations never dip low enough to become pro-proliferative
what are the two ways that tumors can become resistant to therapy
adaptive/evasive and intrinsic
define intrinsic resistance
when the tumor cells are not responsive to a particular therapy due to pre-existing factors. drugs are never effective
define adaptive/evasive resistance
when the tumor cells are initially responsive to therapy, but become resistant due to acquired traits
how does metronomic dosing effect the immune system
decreases the activity of TREG Cells and upregulates dendritic cells and effector cells
what drug is particularly immunologically active during metronomic dosing
cyclophosphamide
what are the drawbacks to metronomic dosing
some drugs have cumulative dose dependent limits (doxarubicin, ect) and can’t be sued for an extended period of time. also, extended therapy is not good in children
what is the typical dosing regimen for acute myeloid leukemia
daunorubicin and ARA-C with or without thioguanine
describe the mechanism of action of Gentuzumab
it is a monoclonal antibody that carries a pharmacologic payload. the antibody is endocytosed and the payload kills the cell. was not approved by the FDA
what is the first line drug for postremission AML
cytarabine
what drives proliferation in acute promyelocitic leukemia
PML/RARA fusion gene
what drugs are useful in APL
ATRA and arsenic tetroxide
how does ATRA work
it drive differentiation and then apoptosis of APL cells
what is the mechanism of action of arsenic tetroxide
degrade PML-RARA fusion protein
what is the black box warning for arsenic tetroxide
CV toxicity
