Cytotoxic Chemotherapy

Question 1

what are the options when a cancer relapses or is resistance to Tx

Answer 1

alternative drugs

intensify dose

Question 2

what are the stages of the cell cycle

Answer 2

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

Question 3

what are the types of cytotoxic drugs

Answer 3

cell cycle specific

non cell cycle specific

Question 4

what are cell cycle specific agents

Answer 4

-antimetabolites (impair nucleotide synthesis/ incorporation)
mitotic spindle inhibitors

Question 5

give examples of antimetabolites

Answer 5

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)

Question 6

give examples of mitotic spindle inhibitors

Answer 6

plant derivatives: niva alkaloids, taxotere

Question 7

what do non cell cyle specific agents target

Answer 7

non tumour specific- damage normal stem cells

cumulative dose more important than duration

Question 8

what are the characteristics of cell specific agents

Answer 8

relatively tumour specific

exposure duration more important than dose

Question 9

give examples of non cell cycle specific agents

Answer 9

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)

Question 10

what are the immediate general side effects of cytotoxic drugs

Answer 10

(affects rapidly diving organs)

• bone marrow suppression
• gut mucosal damage
• hair loss

Question 11

what is a common SE of vinca alkaloids

Answer 11

neuropathy

Question 12

what is a common SE of anthracyclines

Answer 12

cardiotoxicity

Question 13

what is a common SE of cis platinum

Answer 13

nephropathy

Question 14

what are the long term side effects of cytotoxic drugs

Answer 14

aklylating agents: infertility, secondary malignancy

anthracyclies: cardiomyopathy

Question 15

what must chemo drugs be to use them in combo

Answer 15

non cross resistant drug combos
non overlapping toxicity spectra
additive/ synergistic mechanisms of action

Question 16

why does chemo fail

Answer 16

slow tumour doubling time
drug resistant mechanisms (decreased drug accumulation/ altered metabolism, increased DNA repair, altered gene expression)

Question 17

what is intensifying chemotherapy limited by

Answer 17

myelosuppression

Question 18

how do you overcome myelosuppression

Answer 18

haematopoietic growth factors

combine myelosuppressive/ non myelosuppressive agents

intensify dose of active drugs + stem cell rescue

Question 19

where can you source stem cells for transplantation

Answer 19

tissue source: blood versus bone

patient source: autologous, allogenenic: sibling, unrelated

Question 20

what are the stages of progenitor cell transplantation

Answer 20

blood/ bone marrow cell collection (autologous and allogenic)
myeloablative therapy
progenitor cell re-infusion bone marrow regeneration

Question 21

what chromosome has a balanced translocation in CNL

Answer 21

the philadelphia chromosome (22)

Question 22

what drugs for chronic myeloid leukaemia

Answer 22

tyrosine kinase inhibitors