THE PRINCIPLE OF CYTOTOXIC AGENTS IN GYNAECOLOGY

Question 1

T/F: Use of cytotoxic should be restricted to patient in which diagnosis of cancer has been confirmed by either biopsy or cytology

Answer 1

T

Question 2

T/F: In the use of cytotoxic drugs it is important to ascertain whether a patient has measurable disease and / or elevated tumour marker.

Answer 2

T

Question 3

10 hallmarks of cancer

Answer 3

1. Evading growth suppressors
2. Avoiding immune destruction
3. Enabling replicative immortality
4. Tumor-promoting inflammation
5. Activating, invasion and metastasis
6. Inducing angiogenesis
7. Genome instability and mutation
8. Resisting cell death
9. Deregulating cellular energetics
10. Sustaining proliferative signalling

Question 4

6 objectives of cytotoxic chemotherapy

Answer 4

1. To achieve complete cure
2. To achieve best possible survival
3. To relieve agony by palliation in terminal cases
4. To prevent reoccurrence
5. To reasonably reduce distant and regional metastasis and if present, to treat them
6. To improve the result of surgery, radiotherapy and immunotherapy

Question 5

4 chemotherapeutic responses of tumours

Answer 5

1. Highly chemo-sensitive
2. Chemosensitive
3. Low sensitivity
4. Chemo-resistant

Question 6

T/F: Cure is achieved in highly chemosensitive tumors

Answer 6

T

Question 7

2 examples of highly chemosensitive tumors

Answer 7

1. Ovarian germ cell tumors
2. Gestational trophoblastic tumor

Question 8

T/F: Cure is uncommon in chemosensitive tumors

Answer 8

T
Chemotherapy improves survival but does not restore a normal life expectancy

Question 9

Example of a chemosensitive tumor

Answer 9

Epithelial cancer of the ovary with 70-80% response but most patient will have relapse

Question 10

% response of epithelial cancer of the ovary to cytotoxic chemotherapy

Answer 10

70 - 80%

Question 11

Example of tumors with low sensitivity to chemotherapy

Answer 11

Uterine leiomyosarcoma

Question 12

T/F: In tumors with low sensitivity to chemotherapy impact of therapy over survival rate is not clear

Answer 12

T

Question 13

Example of chemoresistant tumor

Answer 13

Metastatic melanoma

Question 14

Response of chemoresistant tumors to cytotoxic chemotherapy

Answer 14

Low or unpredictable response

Question 15

Therapeutic index is —

Answer 15

Quantitative measurement of drug safety

The ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response

Question 16

The ratio of the dose that produces toxicity to the dose that produces a clinically desired or effective response

Answer 16

Therapeutic index

Question 17

T/F: A safer drug has a higher therapeutic index

Answer 17

T

Question 18

3 biological concepts influencing treatment

Answer 18

Cell cycle
Cell kinetics concepts
Cancer cell growth

Question 19

Duration of cycle from M phase to another M phase.

Answer 19

Generation time

Question 20

Maximum variation seen with generation time is in which phase of cell cycle

Answer 20

G0

Question 21

T/F: Dividing cells that are actively traversing the cell cycle are most sensitive to chemotherapy

Answer 21

T

Question 22

The time required to complete the five phases of the cell cycle

Answer 22

The cell generation time

Question 23

Fate of G1 cells

Answer 23

G1 cells may either terminally differentiate into the G0 phase or reenter the cell cycle after a period of quiescence

Question 24

3 activities seen in G1

Answer 24

protein synthesis, RNA synthesis, and DNA repair.

Question 25

T/F: Cells with prolonged G1 are considered to be in the G0 phase

Answer 25

T G0 = resting phase

Question 26

What happens in S phase

Answer 26

New DNA is synthesized

Question 27

T/F: The G2 (premitotic) phase is characterized by cells having twice the DNA content as they prepare for division

Answer 27

T

Question 28

T/F: Actual mitosis and chromosomal division take place during the M phase

Answer 28

T

Question 29

T/F: Tumors have faster generation times

Answer 29

F Tumors do not typically have faster generation times. They instead have many more cells in the active phases of replication and have dysfunctional apoptosis (programmed cell death)

Question 30

T/F: Normal tissues have a much larger number of cells in the G0 phase

Answer 30

T

Question 30

T/F: Normal tissues have a much larger number of cells in the G0 phase

Answer 30

T

Question 31

The human body contains --- number of cells

Answer 31

5 x 10^13 cells

Question 32

At what size do tumor cells become clinically detectable

Answer 32

Tumour becomes clinically detectable when there is a mass of 10^9 cells (1 g)

Question 33

T/F: Cell cycle specific agents are most active in the S phase of the cell cycle

Answer 33

T

Question 33

T/F: Cell cycle specific agents are most active in the S phase of the cell cycle

Answer 33

T

Question 34

What is Gompertzian growth?

Answer 34

This means exponential spurt and exponential growth retardation over entire duration of tumour growth i.e. as the tumour size increases rapidly then the time required in the doubling its size also increases

Question 35

T/F: When a cancer is microscopic and nonpalpable, growth is exponential

Answer 35

T

Question 36

T/F: Chemo therapeutic drugs work by 1st order kinetics

Answer 36

T

Question 37

What is 1st order kinetics

Answer 37

Killing of a constant fraction of cells rather than a constant number

Question 38

T/F: The cure rate of chemotherapeutic drugs will be significantly increased if the tumour mass is small

Answer 38

T

Question 39

6 mechanisms of chemotherapy drug resistance

Answer 39

1. Increased rate of drug deactivation 2. Decreased killing activity of drug 3. Increased drug efflux 4. Decreased drug intake by tumour cells 5. Altered efficacy of inhibiting enzymes 6. Increased production of drug target enzymes

Question 40

What is the GOLDIE COLDMAN HYPOTHESIS

Answer 40

The probability that a given tumor harbors drug-resistant cells at the time of diagnosis is a function of the size of the tumor and the frequency of the mutation