Chemotherapy

Question 1

What is the overriding goal of cytotoxic chemotherapy?

Answer 1

Drugs kill healthy and cancerous cells - goal is to kill the cancer without killing the patient

Question 2

Describe the 5 stages of the cell cycle.

Answer 2

G0: Rest - no cell division
G1: cells inc in size and prep for division
S: synthesis –> DNA replication
G2: checkpoint to confirm everything is in place for cell division
M: mitosis –> division into two cells

Question 3

T/F: All cells eventually move through all five phases of the cell cycle.

Answer 3

False: some cells never divide –> neurons for example

Question 4

List some cells that spend almost no time in the G0 rest phase and state why this is clinically relevant.

Answer 4

Skin cells, uterine lining, lining of the GI tract, bone marrow –> these cells are prone to cancer because they rapidly divide

Question 5

What are the two most important phases in the cell cycle with respect to cancer

Answer 5

G1 and G2 because those are the checkpoints

Question 6

Describe the checkpoint phases (G1 and G2) of the cell cycle and state how this relates to cancer.

Answer 6

Checkpoint phases confirm everything in the cell is working properly. If irregularities are detected, the cell undergoes apoptosis and dies. In cancer cells, the checkpoints fail and the cells divide with the irregularities in place.

Question 7

Describe the mechanism of action of alkylating agents.

Answer 7

Cause irreparable damage to cell DNA independent of which phase of the cell cycle the cell is in.

Question 8

Describe the mechanism of action of antimetabolites.

Answer 8

They work in S phase –> antimetabolites decrease, alter, or interfere with function of nucleotide base pairs inhibiting DNA replication.

Question 9

Describe the mechanism of action of microtubule targeting agents.

Answer 9

They work in M phase –> prevent assembly and disassembly of microtubules, thus inhibiting mitosis.

Question 10

Describe the mechanism of action of topoisomerase targeting agents.

Answer 10

They work in S phase –> stop DNA from being able to unwind and rewind inhibiting DNA replication

Question 11

Describe the mechanism of action of miscellaneous cytotoxic agents.

Answer 11

Many different mechanisms of action with some being cell phase specific and others non-phase specific

Question 12

T/F: Cytotoxic agents kill healthy cells at the same rate they kill cancer cells.

Answer 12

False: They tend to kill cancer cells faster because cancer cells are replicating more quickly.

Question 13

Of healthy cells, which will be affected first by cytotoxic drugs.

Answer 13

Rapidly dividing cells –> bone marrow, GI, hair, etc.

Question 14

Describe how dosing of cytotoxic agents is different than most other drugs.

Answer 14

Typically, drugs are dosed to efficacy - we give as much as possible to have the most positive effect. Cytotoxic drugs are dosed to toxicity - we give the max amount we can give without the drug killing you.

Question 15

For individual patients, how is the dose of cytotoxic drugs generally determined?

Answer 15

Dosed by body surface area rather than actual weight or ideal body weight.

Question 16

How do clinicians choose which class of cytotoxic drug will be used for each patient and why are they selected this way?

Answer 16

Agents from different classes are combined to form a regimen.
This reduces toxicity and resistance.

Question 17

How do clinicians decide when to stop cytotoxic chemotherapy in cancer patients?

Answer 17

Treat beyond disappearance of cancer on PET scan. Undetectable cancer cells often remain after PET scan is clear.

Question 18

Describe tumor lysis syndrome and state the most common clinical sequelae from chemotherapy.

Answer 18

When large volume of tumor cells die, they release large volumes of K, phosphorus, Ca, uric acid, etc.
Increased uric acid causes gout –> renal function also affected.

Question 19

What classes of medications are used to treat chemotherapy toxicity?

Answer 19

Antiemetics, colony stimulating factors (increase formation of bone marrow cells)

Question 20

What cautions must be considered when administering cytotoxic chemotherapy?

Answer 20

Administer IV chemotherapy via a central line
Neutrophils < 1500 is a relative contraindication - chemotherapy causes neutropenia
Caution when prescribing NSAIDs, APAP, anticoagulants

Question 21

Describe vesicant chemotherapy and state which caution this impacts.

Answer 21

Vesicants destroy epidermis on contact. They are given in central lines with greater flow so they are diluted rapidly.

Question 22

Describe the timeline progression of neutropenia following cytotoxic chemotherapy administration.

Answer 22

Neutrophils start to decline after day 3-5, reach a nadir at day 7-10, and return to normal around day 17-21.

Question 23

Which steroid may be used as an antiemetic in chemotherapy pateints?

Answer 23

Dexamethasone

Question 24

Describe the mechanism of tyrosine kinase inhibitors.

Answer 24

Blocks tyrosine kinase site on a growth factor receptor preventing growth of the cancer cells.

Question 25

Describe the mechanism of monoclonal antibodies.

Answer 25

Bind extracellular proteins on the cell surface --> usually growth factor receptors.

Question 26

Describe the mechanism of immune modulating agents (IMIDs).

Answer 26

Stimulate or inhibit the immune system depending on what cancer is being targeted.

Question 27

Describe the mechanism of MTOR inhibitors.

Answer 27

MTOR is an intracellular receptor that stimulates cellular metabolism and other cell functions.

Question 28

T/F: Tyrosine kinase inhibitors only affect cancer cells and have no impact on healthy cells.

Answer 28

False: They will likely impact healthy cells. But cancer cells have more growth factor receptors. So the impact on healthy cells is negligible compared to cancer cells.

Question 29

What is another name for targeted therapy agents and how is this clinically relevant?

Answer 29

Cytostatic agents because they mostly inhibit cancer cell growth signals. They prevent tumor growth rather than destroying the tumors. Only cytotoxic agents destroy tumors.

Question 30

Describe how cytostatic drugs are administered?

Answer 30

They are usually given continuously rather than in on-off cycles like cytotoxic agents.

Question 31

What are the common routes of administration of cytostatic agents?

Answer 31

Mostly PO. Some are given IV q week.

Question 32

Other than simply being targeted agents, state why cytostatic agents are less toxic than cytotoxic agents.

Answer 32

They are dosed based on efficacy as opposed to cytotoxic agents which are dosed to toxicity.

Question 33

Which healthy cells are most likely to be impacted by cytostatic agents?

Answer 33

Rapidly dividing healthy cells --> skin effects (rashes) are most common.

Question 34

T/F: Cytostatic agents have a lot of drug interactions.

Answer 34

True: Almost all cytostatic agents are metabolized by CP-450

Question 35

When administering cytostatic agents, should you be concerned about monitoring renal or liver function?

Answer 35

Both - may need to adjust dose based on either liver or kidney dysfunction.

Question 36

What are the common AEs associated with cytostatic agents?

Answer 36

EGFR - receptor blocked by cytostatic agents that cause skin rashes and other effects (including conjunctivitis and dry eyes) VEGF - receptor blocked by cytostatic agents that inhibits angiogenesis

Question 37

Why is the inhibition of angiogenesis by cytostatic agents be both an AE and a benefit?

Answer 37

Tumors rely on angiogenesis for growth. | Our bodies rely on angiogenesis to repair damaged vessels. Results in increased bleeding, thrombosis, and HTN.

Question 38

Which cytostatic agent is also used to treat rheumatoid arthritis?

Answer 38

Rituximab

Question 39

T/F: Use of cytostatic agents has replaced the need for cytotoxic agents.

Answer 39

False: Cytostatic agents are rarely used alone because they don't eliminate existing tumors. Only in very early stages of a cancer might cytostatic agents alone be used.