Cytotoxic Chemotherapy

Question 1

How does chemo and radiotherapy work?

Answer 1

Question 2

How can we classify cytotoxic drugs?

Answer 2

cell cycle specific
Non cell cycle specific

Question 3

What are cell cycle specific agents?

Answer 3

Tumour specific
Duration of exposure more important than dose

Question 4

Give examples of cell cycle specific agents

Answer 4

Antimetabolites - impair nucleotide synthesis / incorporation

Mitotic spindle inhibitors

Question 5

What antimetabolite chemotherapy drugs are there?

Answer 5

Methotrexate - inhibits dihydrofolate reductease

6-Mercaptopurine / Cytosine arabinside / Fludarabine . incoporated into DNA

Hydroxyurea - impaired DNA synthesis (ribonucleoide reductase)

Question 6

Describe cell cycle associated enzymes as chemotherapeutic targets

Answer 6

Question 7

What mitotic spindle inhibitors are there?

Answer 7

Vinca alkaloids - vincristine / vinblastine
Taxotere (taxol)

Question 8

What are characteristics of non cell cycle specific agents?

Answer 8

Non tumour specific; damage normal stem cells

Cumulative dose more important than duration

Question 9

What are examples of non cell cycle specific agents?

Answer 9

Alkylating agents - chlorambucil / melphalan; bind covalently to bases of DNA (adducts); produces DNA strand breaks (mutation) by free radical production

Platinum derivatives - cisplatinum / carboplatin

Cytotoxic antibiotics
- anthracyclines: daunorubicin / doxorubicin / idarubicin
- DNA intercalation: reversible
- Impairs RNA transcription
- Strand breaks in DNA (free radicals)

Question 10

What are general immediate side effects of cytotoxic drugs?

Answer 10

Affects rapidly dividing organs

Bone marrow suppression
Gut mucosal damage
Hair loss (alopecia)

Question 11

What are examples of drug specific side effects?

Answer 11

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

Question 12

What are long term side effects of cytotoxic drugs?

Answer 12

Alkylating agents- infertility, secondary malignancy

Anthracyclines - cardiomyopathy

Question 13

What are combination chemotherapy?

Answer 13

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

Question 14

Why does chemotherapy fail?

Answer 14

Question 15

What is intensifying chemotherapy limited by? How is it overcome?

Answer 15

By myelosuppression

Overcome by:
use haematopoietic growth factors
combine myelosuppressive / non-myelosuppressive agents
intensify doses of active drugs (log-linear tumour kill) + stem (progenitor) cell rescue

Question 16

What are sources of stem cells for transplantation?

Answer 16

Tissue source - blood versus bone marrow

Patient source - autologous, allogenic (sibling, unrelated)

Question 17

How does progenitor cell transplantation work?

Answer 17