25. Management of Chemotherapy Toxicities

Question 1

this type of nausea/vomiting occurs despite prophylactic treatment and/or requires rescue

Answer 1

breakthrough nausea/vomiting

Question 2

this type of nausea/vomiting occurs during subsequent cycles when antiemetic prophylaxis and/or rescue have failed in earlier cycles

Answer 2

refractory nausea/vomiting

Question 3

explain the pathophysiology of acute CINV

Answer 3

in acute CINV, free radicals from toxic chemo stimulate the enterochromaffin cells in the GI tract, causing the release of serotonin. serotonin then binds to intestinal vagal afferent nerves via 5-HT3 receptors which trigger the chemoreceptor trigger zone in the CNS

Question 4

explain the pathophysiology of delayed CINV

Answer 4

substance P is the primary transmitter involved in delayed CINV. chemo drugs trigger the release of substance P from neurons in the central and peripheral nervous systems, which then binds to NKI receptors to induce vomiting

Question 5

this type of CINV is very amendable to drug therapy. the primary mediator is serotonin and occurs within 24 hours of chemotherapy

Answer 5

acute

Question 6

this type of CINV has a variable response to drug therapy. the mechanism is not fully understood and occurs after 24 hours to up to one week after chemotherapy

Answer 6

delayed

Question 7

this type of CINV occurs before patients receive their chemotherapy, after a prior negative experience with chemotherapy (nausea > vomiting)

Answer 7

anticipatory

Question 8

what are some treatment-specific risk factors for N/V

Answer 8

• emetogenicity of chemo agent
• tumor burden
• combo of chemo agents
• combined modality therapy
• rapid infusion rate
• repetitive daily doses

Question 9

what are some patient-specific risk factors for N/V

Answer 9

• children > adults
• women > adults
• alcohol history
• hx of morning sickness
• hx of motion sickness
• prior CINV
• depression and anxiety

Question 10

what are some clinical consequences of CINV

Answer 10

• metabolic derangements
• nutritional depletion and anorexia
• deterioration of patients physical and mental status
• degeneration of self-care and functional ability
• d/c therapy***

Question 11

these agents can be given as a single dose prior to chemo.
- be careful with Qt prolongation

Answer 11

5HT3 antagonists (e.g. Ondansetron)

Question 12

this newer agent has a strong binding affinity for 5HT3 with a long plasma half-life of 40 hours therefore effective in both acute and delayed CINV

Answer 12

Palonosetron

Question 13

what agent should always be given with a 5-HT3 antagonist before chemotherapy

Answer 13

dexamethasone

Question 14

true or false: if a patient is getting Palonosetron instead of another 5HT3 antagonist, their dose of dexamethasone would need to be increased

Answer 14

false - Palonosetron is dexamethasone sparing therefore can cut back on doses of dexamethasone with this agent

Question 15

list the NK1 receptor antagonsits

Answer 15

• Aprepitant
• Fosaprepitant
• Netupitant

Question 16

what CYP enzymes to Aprepitant/Fosaprepitant/Netupitant induce or inhibit

Answer 16

• moderate inhibitor of CYP3A4 (therefore if administered with dexamethasone, decrease dex dose by 50%)
• weak inducer of CYP2C9 (can affect warfarin)

Question 17

this is a second generation AP that blocks 5HT2 receptors and D2 receptors and may be partially useful for the prevention of acute and delayed CINV (preferred for breakthrough CINV?)

Answer 17

olanzapine

Question 18

if a patient is on an HEC chemo drug, what agents should be given pre-chemo for nausea?

Answer 18

1. dexamethasone 8-12 mg PO
2. NK1
3. 5HT3 antagonist

Question 19

if a patient is on a HEC chemo drug, what agents should be given post-chemo for nausea?

Answer 19

1. dexamethasone 4 mg PO the evening of chemo then BID for 2-4 days
2. +/- prochlorperazine or metoclopramide as needed

Question 20

if a patient is on an MEC chemo drug, what agents should be given pre-chemo for nausea?

Answer 20

1. dexamethasone 8-12 mg PO
2. 5HT3 antagonist

Question 21

if a patient is on an MEC chemo drug, what agents should be given post-chemo for nausea?

Answer 21

1. dexamethasone 4 mg PO the evening of chemo then BID for 2-3 days
2. +/- prochlorperazine or metoclopramide as needed

Question 22

if a patient is on a low emetogenicity chemo drug, what agents should be given for nausea?

Answer 22

maybe something pre-chemo and maybe something post-chemo