Fitz-Antineoplastics I

Question 1

What are the distinguishing features of cancer?

Answer 1

DNA disease- no tx to address fundamental problem
Rapidly dividing cells don’t die when they’re supposed to (increased oncogene or decreased TSG)
Derived from normal tissue

Question 2

What is differential sensitivity?

Answer 2

You want tx to affect cancer cell more than normal tissue

Question 3

What are the processes targeted by antineoplastic drugs?

Answer 3

rapidly dividing cells
angiogenesis
lack of differentiation
lack of immune response
cell markers
defective gene products

• moving from least specific to most specific (most SE to fewest)

Question 4

What cells are affected by cytotoxic drugs?

Answer 4

Cancer
bone marrow
GI mucosa--> N and V
Hair follicles--> allopecia
Fetus
Radiation recall reaction

Question 5

What cell is related to the major dose limiting complication?

Answer 5

Cytotoxic drugs affect bone marrow, and can increase susceptibility to infections. This is why chemo is given in cycles.

Question 6

CCS drugs are most effective in fast or slow growing cancers?

Answer 6

fast

Question 7

How do CCNS drugs use recruitment?

Answer 7

CCNS drugs can recruit cells to enter cell cycle to then kill w/ a CCS drug

Question 8

CCS vs. CCNS

What phase do they act in?

Answer 8

CCS: specific phase
CCNS: primary action is anytime but cells die during specific phase

Question 9

What are examples of CCS drugs and where do they act?

Answer 9

G2/M- plant alkaloids

S- anti- metabolites

Question 10

What are examples of CCNS drugs?

Answer 10

alkylating agents

anthracyclins

Question 11

CCS drugs target…

Answer 11

proliferating cells w/ HIGH GROWTH FRACTION

Question 12

CCNS drugs target…

Answer 12

both rapidly and slowly dividing cells

Question 13

CCS vs. CCNS

Which is schedule dependent and which is dose dependent?

Answer 13

CCS: the schedule is more impt than the dose

CCNS: dose more impt than the schedule

Question 14

What is the cell kill hypothesis?

Answer 14

The actions of CCS drugs follow first order kindetics: a given dose kills a constant PROPORTION of a tumor cell population.

This means that the magnitude of the kill is LOGARITHMIC.

Question 15

What are the critical points to remember related to drug therapies?

Answer 15

Earlier is better (lower burden of TCs)
More freq, higher doses
Continue tx past detection pt

Question 16

What are the 5 factors affecting outcome related to the cancer?

Answer 16

Growth fraction
Doubling time
type
stage
resistance

Question 17

What are the 6 factors affecting outcome related to the pt?

Answer 17

Performance status (K...scale)
Bone marrow capacity
Liver/kidney fxn--> elimination
age
compliance

Question 18

What is primary resistance?

Answer 18

An inherent characteristic of cancer cells prevent the drugs from working.

Question 19

What is acquired resistance?

Answer 19

Cancer cells become resistant during tx

Question 20

What is multi-drug resistance?

Answer 20

when tumor cells become cross-resistant to a wide range of chemically dissimilar agents after exposure to a SINGLE drug

Question 21

What are the contributing causes to drug resistance?

Answer 21

Poor distribution
Sanctuary sites
CCS–> cells not in cycle
Cancers are heterogenous

Question 22

What are the mechanisms of drug resistance?

Answer 22

1. Change the MOA of a drug (increase DNA repair, form trapping agents, change target protein)
2. Affect the concentration in the cancer cell (decrease accumulation/activation, or increase inactivation)