Cytotoxic & supportive therapy

Question 1

what is the definition of remission in malignancy?

Answer 1

In complete remission, all signs and symptoms of cancer have disappeared, although cancer still may be in the body.

Question 2

give the two classifications of cytotoxic drugs

Answer 2

Cell cycle specific

non-cell cycle specific

Question 3

what are the general characteristics of cell cycle specific agents?
-give the 2 categories?

Answer 3

tumour specific
the duration of exposure is more important than the dose

-antimetabolites (impair nucleotide synthesis/incorporation)

mitotic spindle inhibitors

Question 4

Give the names and action of 3 antimetabolite drugs?

Answer 4

Methotrexate
inhibits dihydrofolate reductase

6-Mercaptopurine/cytosine arabinoside/Fludarabine
incorporated into DNA

Hydroxyurea
impaired deoxynucleotide synthesis

Question 5

Name 2 mitotic spindle inhibitors?

Answer 5

Vinca alkaloids e.g. Vincristine

Taxotere

Question 6

give the general characteristics of non-cell cycle specific agents?

Answer 6

non-tumour specific, damage normal stem cells

Cumulative dose more important than duration

Question 7

Give the names and mode of action of 3 non-cell cycle specific agents?

Answer 7

Alkylating agents
e.g. chlorambucil/melphalan
these bind covalently to bases of DNA and causes breaks in DNA strand due to free radical production

Platinum derivatives
Cis-platinum/carboplatin

cytotoxic antibiotics
anthracyclines: daunorubicin/doxorubicin/idarubicin
they cause reversible DNA intercalation
impairs RNA transcription and DNA stand breaks

Question 8

What are the SE of cytotoxic drugs?
Immediate effects
-In general? (3)
-vinca alkaloids?
-Anthracyclines?
-Cis-platinum ?
Long term
-alkylating agents? 
-Anthracyclines?

Answer 8

-BM suppression (infection)
gut mucosal damage
Hair loss

• neuropathy
• cardiotoxicity
• nephrotoxicity
• infertility, secondary malignancy
• cardiomyopathy

Question 9

what 3 criteria must be met by the drugs used in combination chemo? (3)

Answer 9

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

Question 10

Why does chemotherapy fail? (4)

Answer 10

slow tumour doubling times

tumour sanctuaries (CNS and testes)

drug resistance

P53 mutation- P53 is the guardian of the genome mediates apoptosis so if it is not functioning properly then the DNA damage caused by chemo drugs does not cause cell destruction

Question 11

Give 4 ways in which tumour cells can develop drug resistance?

Answer 11

decreases drug accumulation via MDR-1/PGP
altered drug metabolism
Increased DNA repair
Altered gene expression

Question 12

what limits the intensification of chemotherapy?

-how is this overcome? (3)

Answer 12

myelosuppression

-use haematopoitic growth factors
combine myelosuppressive/non-myelosppressive agents
intensify doses of active drugs + stem cell rescue (i.e. store BM when patient in remission after killing malignancy cells with highly ablative chemo)

Question 13

give the different sources of stem cells for transplantation

Answer 13

blood vs bone marrow

Autologous (patient’s own cells) vs Allogenic (donor)

Question 14

• indication for use of autologous stem cells?

- indication for use of allogenic stem cells?

Answer 14

• induce blood count recovery after myeloablative doses of chemo
• after myeloablative chemo looking for a graft vs malignancy effect

Question 15

what does the philadelphia chromosome cause?

Answer 15

chronic Myeloid leukaemia