Cytotoxic and Supportive Therapy

Question 1

What is the cytotoxic drug classification?

Answer 1

Cell cycle specific

Non-cell cycle specific

Question 2

What are general characteristics of cell cycle specific agents?

Answer 2

Tumour specific (relatively)
Duration of exposure more important than doseq

Question 3

What do antimetabolites do?

Answer 3

Impair nucleotide synthesis/incorporation

Question 4

What are some examples of cell cycle specific agents?

Answer 4

Antimetabolites

Mitotic spindle inhibitors

Question 5

What are some antimetabolites?

Answer 5

Methotrexate- inhibits dihydrofolate reductase
6-Mercaptopurine / Cytosine arabinoside / Fludarabine- incorporated into DNA
Hydroxyurea- impaired deoxynucleotide synthesis (ribonucleotide reductase)

Question 6

What are some examples of mitotic spindle inhibitors?

Answer 6

Vinca alkaloids- vincristine/vinblastine

Taxotere (Taxol)

Question 7

What are general characteristics of non-cell cycle specific agents?

Answer 7

Non tumour specific- damage normal stem cells

Cumulative dose more important than duration

Question 8

What are some examples of non-cell cycle specific agents?

Answer 8

Alkylating agents
Platinum derivatives- cis-platinum/carboplatin
Cytotoxic antibiotics

Question 9

Describe alkylating agents

Answer 9

Chlorambucil / melphalan
Bind covalently to bases of DNA (adducts)
Produces DNA strand breaks (mutation) by free radical production

Question 10

Describe cytotoxic antibiotics

Answer 10

Anthracyclines: daunorubicin / doxorubicin / idarubicin
DNA intercalation: reversible
Impairs RNA transcription
Strand breaks in DNA (free radicals)

Question 11

What are the immediate general side effects of cytotoxic drugs?

Answer 11

Affects rapidly dividing organs
Bone marrow suppression
Gut mucosal damage
Hair loss (alopecia)

Question 12

What are some examples of cytotoxic drug specific side effects?

Answer 12

Vinca alkaloids: neuropathy
Anthracyclines: cardiotoxicity
Cis-platinum: nephrotoxicity

Question 13

What are the long term side effects of cytotoxic drugs?

Answer 13

Alkylating agents: infertility, secondary malignancy

Anthracyclines: cardiomyopathy

Question 14

Describe combination chemotherapeutic regimens

Answer 14

Non-cross resistant drug combinations
Non-overlapping toxicity spectra
Additive/synergistic mechanisms of action

Question 15

Why does chemo fail?

Answer 15

Slow tumour doubling time
Tumour sanctuaries
Drug resistant mechanisms:
decreased drug accumulation; MDR-1 / PGP
altered drug (pro-drug) metabolism: cyclophosphamide
increased DNA repair; cis-platinum resistance
altered gene expression: reduced topoisomerase II

Question 16

How do you intensify chemo (limited by myelosuppression)?

Answer 16

Use haematopoietic growth factors
Combine myelosuppressive / non-myelosuppressive agents
Intensify doses of active drugs (log-linear tumour kill) + stem (progenitor) cell rescue

Question 17

What are sources of stem cells for transplantation?

Answer 17

Tissue source- blood versus bone marrow

Patient source- autologous, allogenic- sibling/unrelated

Question 18

What occurs in progenitor cell transplantation?

Answer 18

Autologous/allogenic collection
Myeloablative therapy
Progenitor cell reinfusion
Bone marrow regeneration