Cytotoxic Chemotherapy Flashcards
what are the options when a cancer relapses or is resistance to Tx
alternative drugs
intensify dose
what are the stages of the cell cycle
G1- cellular contents except chromosomes are duplicated (cell growth)
(G0 cell cycle arrest)
S- chromosomes duplicates
G2- duplicated chromosomes double checked, growth and prep for mitsosis
mitosis
cytokinesis
what are the types of cytotoxic drugs
cell cycle specific
non cell cycle specific
what are cell cycle specific agents
-antimetabolites (impair nucleotide synthesis/ incorporation)
mitotic spindle inhibitors
give examples of antimetabolites
methotrexate
6-mercaptopurine/ cytosine arabinoside/ fludarabine
hydroxyurea
also drugs can target the cell cycle associated enzymes (act on folate metabolism, nucleotide synthesis, unwinding of DNA)
give examples of mitotic spindle inhibitors
plant derivatives: niva alkaloids, taxotere
what do non cell cyle specific agents target
non tumour specific- damage normal stem cells
cumulative dose more important than duration
what are the characteristics of cell specific agents
relatively tumour specific
exposure duration more important than dose
give examples of non cell cycle specific agents
alkylating agents (chromabucil- bind to DNA bases, produces strand breaks)
platinum derivatives (cis-platinum/ carboplatin)
cytotoxic antibiotics (anthracyclines: -icin, DNA intercalation, impairs RNA transcription, strands break in DNA)
what are the immediate general side effects of cytotoxic drugs
(affects rapidly diving organs)
- bone marrow suppression
- gut mucosal damage
- hair loss
what is a common SE of vinca alkaloids
neuropathy
what is a common SE of anthracyclines
cardiotoxicity
what is a common SE of cis platinum
nephropathy
what are the long term side effects of cytotoxic drugs
aklylating agents: infertility, secondary malignancy
anthracyclies: cardiomyopathy
what must chemo drugs be to use them in combo
non cross resistant drug combos
non overlapping toxicity spectra
additive/ synergistic mechanisms of action
why does chemo fail
slow tumour doubling time
drug resistant mechanisms (decreased drug accumulation/ altered metabolism, increased DNA repair, altered gene expression)
what is intensifying chemotherapy limited by
myelosuppression
how do you overcome myelosuppression
haematopoietic growth factors
combine myelosuppressive/ non myelosuppressive agents
intensify dose of active drugs + stem cell rescue
where can you source stem cells for transplantation
tissue source: blood versus bone
patient source: autologous, allogenenic: sibling, unrelated
what are the stages of progenitor cell transplantation
blood/ bone marrow cell collection (autologous and allogenic)
myeloablative therapy
progenitor cell re-infusion bone marrow regeneration
what chromosome has a balanced translocation in CNL
the philadelphia chromosome (22)
what drugs for chronic myeloid leukaemia
tyrosine kinase inhibitors
