Lecture 20: Principles of cancer therapy

Question 1

What is chemotherapy?

Answer 1

• Using chemicals to kill disease causing cells in the body i.e bacteria, fungi, viruses and cancer

Question 2

What is drug therapy in contrast to chemotherapy?

Answer 2

• Using chemicals to modulate body processes

i. e BP, mood

Question 3

Describe selective toxicity:

Answer 3

• Selective toxicity is the goal of cancer chemotherapy
• Occurs when toxicity is produced in the cancer cell without (or with less) effects in the host cells (of drug therapy)
• Achieved by exploiting differences between host cells and diseased producing cells.

Question 4

What are some disease cell characteristics exploited in selective toxicity?

Answer 4

• There is a unique target in the pathogen
• The target is structurally different in the pathogen
• The target is functionally different in the host

Question 5

What is therapeutic index?

Answer 5

• Important indicator of selective toxicity

- Ratio of dose required to produce a toxic effect divided by the dose required to produce desired effect

Question 6

Classification of cancer chemotherapy drugs; according to mode of action. What are the 8 categories?

Answer 6

1. Alkylating agents
2. Platinum based drugs
3. Antimetabolites
4. Topoisomerase interactive drugs
5. Anti-microtubule drugs
6. Hormonal agents
7. Target therapies
8. Vascular targeting therapies

Question 7

Whats the action of cyclophosphamide

Answer 7

Alkylating agents

• Binds DNA
• i.e Cyclophosphamide

Question 8

Whats the action of cisplatin

Answer 8

Platinum based drugs

• Binds DNA
• i.e Cisplatin

Question 9

Whats the action of methotrexate

Answer 9

Antimetabolites

• Inhibit DNA synthesis
• i.e Methotrexate

Question 10

Whats the action of doxorubicin

Answer 10

Topoisomerase-interactive drugs

• Inhibit topoisomerases
• i.e doxorubicin

Question 11

Whats the action of paxilatcel

Answer 11

Antimicrotubule drugs

• Bind microtubules
• i.e paxlitacel

Question 12

Whats the action of Tamoxifen?

Answer 12

Hormonal agents

• Blocks production or action of sex steroids
• i.e Tamoxifen

Question 13

Whats the action of imatinib?

Answer 13

Target therapies

• Block oncogenic proteins
• i.e imatinib

Question 14

Whats the action of bevacizumab?

Answer 14

Vascular targeting therapies

• Inhibit angiogenesis
• i.e bevacizumab

Question 15

Whats the first order kinetics of tumour growth and whats the implication for chemo?

Answer 15

Cancer cells double at a constant rate

Chemo kills only a portion of cells , thus repeated doses required, continued once no longer clinically evident for this reason

Question 16

What is the criteria for combination chemotherapy?

Answer 16

• More effective than using a single agent

Criteria:

• Some activity as a single agent
• Differing mechanisms of action
• Different side effect profiles

Question 17

What is the BEP combination chemotherapy for testicular cancer?

Bicomycin
Etoposide
cisPlatin

Answer 17

• Bicomycin: Induces DNA breaks; toxic in lungs
• Eptoposide: Topoisomerase 2 poison, toxic to bone marrow
• Cisplatin: Induces DNA crosslinks, toxic to peripheral nerves

Question 18

What are some adverse effects from chemo?

Answer 18

• > Antiproliferative ; Myelosuppresion, mucositis, alopecia, sterility
• > Mutagenesis: Secondary cancers, teratogenicity
• > Microtubule disturbance; Peripheral neurotoxicity
• > Sex steroid deficiency; Decrease labido, flushing

Question 19

What are some indications for cancer chemotherapy:

Answer 19

• Curative (those cancers that respond well)
• With surgery (additive)
• With radiotherapy
• Palliation; prolong survival