Introduction to Chemotherapy

Question 1

What are the 3 main goals/objectives of cancer treatment?

Answer 1

1. Cure the patient (kill or remove ALL cancer cells)
2. Prolong patient survival (kill MOST cancer cells)
3. Palliate symptoms (kill SOME cancer cells)

Question 2

What is chemotherapy in a clinical context?

Answer 2

Drugs that target cancer cells.

Question 3

When is chemotherapy used?

Answer 3

1. For patients with advanced disease where no other treatment exists.
2. Adjuvant chemotherapy: systemic treatment following local radiotherapy or surgery to control microscopic metastasis.
3. Primary or Neo-adjuvant chemotherapy: as initial therapy for locally advanced cancer to render it more amenable to subsequent surgery.

Question 4

Why might patients relapse after apparently being cured?

Answer 4

Microscopic metastasis or resistant cells.

Question 5

What does chemotherapy target and why is this a disadvantage?

Answer 5

Targets cell replications in cancer cells AND normal cells, which can kill healthy cells.

Question 6

What is the resting phase of the cell cycle?

Answer 6

G0.

Question 7

In which phase is DNA replicated?

Answer 7

S.

Question 8

What is the pre-mitotic phase of the cell cycle?

Answer 8

G2.

Question 9

What is mitosis in the cell cycle?

Answer 9

M.

Question 10

What are cell cycle specific drugs?

Answer 10

They target specific points in the cell cycle.

Examples include:
- S phase: antimetabolites, topoisomerase inhibitors
- G0 phase: micro-tubule inhibitors, topoisomerase inhibitors, alkylating agents.

Question 11

What assumptions do we make about chemotherapy?

Answer 11

1. Heterogeneous nature of tumors.
2. Dosage response varies due to heterogeneity.
3. Patients can become intolerant to chemotherapy.
4. Different drugs have different kill properties.

Question 12

What is the log-kill kinetics model?

Answer 12

Every dose of chemotherapy kills a certain proportion of cells, and cancer cells can grow between cycles.

Question 13

Describe tumor kinetics.

Answer 13

1. Initial slow phase.
2. Exponential growth.
3. Plateau phase as nutrients and oxygen are exhausted.

Question 14

Why is adjuvant chemotherapy effective?

Answer 14

It targets rapidly growing cancer cells during the initial slow growth phase.

Question 15

When is clinical detection usually made and what is the consequence?

Answer 15

Detection is usually in the plateau phase, meaning the cancer is no longer growing quickly.

Question 16

What is the principle of dose intensity?

Answer 16

Giving less time between doses.

Question 17

What limits the use of the dose intensity hypothesis?

Answer 17

Normal cells, especially bone marrow cells, need time to recover.

Question 18

How are chemotherapy agents classified?

Answer 18

Based on mechanism of action.

Question 19

What are the types of chemotherapy agents?

Answer 19

1. Alkylating agents.
2. Platinum agents.
3. Antimetabolites.
4. Topoisomerase inhibitors.
5. Anti-microtubular agents.
6. Other agents.
7. Molecular targeted agents.

Question 20

What is the mechanism of alkylating agents?

Answer 20

They form covalent adducts, transferring alkyl groups to DNA bases, resulting in single or double strand breaks.

Question 21

What is the specificity of alkylating agents?

Answer 21

Limited cell cycle specificity as they bind directly to DNA.

Question 22

What are the types of alkylated adducts?

Answer 22

1. N7 guanine adducts.
2. O6 guanine adducts.
3. Phosphate adducts.

Question 23

What is the mechanism of platinum agents?

Answer 23

They bind covalently to purine DNA bases, resulting in bifunctional intrastrand cross-links that prevent DNA from separating.

Question 24

What is the specificity of platinum agents?

Answer 24

Not S phase specific.

Question 25

What are the side effects of platinum agents?

Answer 25

Nephrotoxicity and resistance.

Question 26

What is the mechanism of antimetabolites?

Answer 26

They interfere with the incorporation of nucleic acid bases, acting as false bases or preventing folate formation.

Question 27

What is the specificity of antimetabolites?

Answer 27

S phase specific.

Question 28

What normal cells in the body have a high turnover rate?

Answer 28

Bone marrow and gastrointestinal cells.

Question 29

What is an advantage of antimetabolites?

Answer 29

They do not interact with DNA directly, reducing the risk of late carcinogenesis.

Question 30

What is the mechanism of topoisomerase inhibitors?

Answer 30

They inhibit the re-ligation of DNA strands, resulting in single and double strand breaks.

Question 31

What are examples of topoisomerase inhibitors?

Answer 31

Topoisomerase I inhibitors and topoisomerase II inhibitors.

Question 32

What is the mechanism of anti-microtubular agents?

Answer 32

They prevent spindle formation, inhibiting cell cycle progression.

Question 33

What are the two classes of anti-microtubular agents?

Answer 33

1. Taxanes. 2. Vinca alkaloids.

Question 34

What are the objectives of combined chemotherapy?

Answer 34

1. More effective than using one drug alone. 2. Provide maximum cell kill within tolerable toxicity for each drug. 3. Broaden coverage of resistant cells in a heterogeneous tumor population.

Question 35

What are the 2 classes of anti-microtubular agents?

Answer 35

Taxanes and vinca alkaloids.

Question 36

What are the combined chemotherapy objectives?

Answer 36

1. Provide maximum cell kill within the toxicity that can be tolerated for each drug. 2. Provide a broader range of coverage of resistant cells in a heterogeneous tumour population. 3. Prevent or slow the development of drug-resistant cells.

Question 37

What are the principles when selecting a combination of chemotherapy agents?

Answer 37

1. Select drugs with different mechanisms of action. 2. Use drugs with different dose-limiting toxicities to minimize damage to any one organ system. 3. Administer in optimum dose & schedule. 4. Maintain minimum interval between cycles. 5. Monitor response, performance & toxicity.

Question 38

Does chemotherapy have a low or high therapeutic index?

Answer 38

Low, hence the toxicity.

Question 39

What is the limiting factor of chemotherapy?

Answer 39

Toxicity to normal cells.

Question 40

How is chemotherapy dosage calculated?

Answer 40

Based on body surface area or renal function. Adjust dose based on individual tolerance.

Question 41

What are the 2 classes of side effects people can get from chemotherapy?

Answer 41

Reversible and irreversible.

Question 42

What are some irreversible side effects of chemotherapy?

Answer 42

Kidney, heart, lungs, and nerves.

Question 43

How do we know treatment is working?

Answer 43

Generally rely on imaging/scans using internationally agreed data, i.e., RECIST.

Question 44

What does a 30% reduction in tumor size indicate?

Answer 44

Partial response.

Question 45

What does a growth of >20% in tumor size indicate?

Answer 45

Progression.

Question 46

What does stable disease mean in terms of tumor size?

Answer 46

Anything between a 30% reduction and a >20% growth.

Question 47

What does a complete response mean in cancer treatment?

Answer 47

Can't see cancer on scan.

Question 48

What may be concealed by a 'complete response' in chemotherapy?

Answer 48

Resistant cells that may cause relapse of apparently cured patients.