Therapeutics Exam 2 (Supportive Care) Flashcards

(283 cards)

1
Q

What is the most feared complication of chemotherapy?

A

Chemotherapy Induced Nausea and Vomiting (CNV)

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2
Q

What are the 5 types of Nausea/Vomiting?

A

Anticipatory
Acute
Delayed
Breakthrough
Refractory

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3
Q

What is anticipatory nausea/vomiting?

A

-A learned response conditioned by previous emetic reactions from prior cycles of chemotherapy
-Can be provoked by sight, sound, or smell

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4
Q

What is acute nausea/vomiting?

A

-Emetic response that correlates with the administration of chemotherapy

within 24 hours of receiving chemotherapy

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5
Q

What is delayed nausea/vomiting?

A

-Related to chemotherapy but occurs >24 hours after completion

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6
Q

What is breakthrough nausea/vomiting?

A

Occurs even though the patient is on scheduled anti-emetics prior to chemotherapy

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7
Q

What is refractory nausea/vomiting?

A

Persists despite appropriate anti-emetic therapy
-Patient has failed other therapies at this point

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8
Q

How does chemotherapy cause CINV?

A

It begins in the GI tract where cytotoxic chemotherapy induces damage to epithelial cells lining the GI tract

Enterochromaffin cells that line the GI tract contain large amounts of serotonin which is released in massive quantities

The chemoreceptor trigger zone (CTZ) stimulates the vomiting center (located in the medulla)

Input to the vomiting center from higher cortical centers such as the pharynx and GI tract induce emesis

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9
Q

Which cells are responsible for the massive release of serotonin in the GI tract after chemotherapy that leads to CINV?

A

Enterochromaffin cells

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10
Q

Which neurotransmitter can be targeted to treat breakthrough CINV?

A

Dopamine

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11
Q

What are the 2 most commonly targeted neurotransmitters for treatment of CINV?

A

Serotonin
Substance P

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12
Q

Which receptor mediates the action of substance P?

A

neurokinin-1 receptor

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13
Q

Which chemotherapy produces the most nausea?

A

Cisplatin

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14
Q

How does the combination of chemotherapies affect emetogenicity?

A

Level 1 and 2 agents do not contribute to the regimen’s emetogenicity

Level 3 and 4 agents increase the emetogenicity of the combination regimen by 1 level per agent

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15
Q

Who is at a higher risk for CINV: Men or Women?

A

Women

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16
Q

Who is at a higher risk for CINV: Younger Patients or Older Patients

A

Younger Patients

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17
Q

What are 4 risk factors of CINV?

A

Prior history of motion sickness

Prior history of morning sickness

Previous CINV

Anxiety/high pretreatment anticipation of nausea

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18
Q

What trait can be protective against CINV?

A

Chronic ethanol use

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19
Q

How do we decide what prophylaxis to use for acute nausea and vomiting?

A

It is based on the emetogenic potential of the chemotherapy

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20
Q

Which is more efficacious: Oral or IV CINV prophylaxis

A

NEITHER, their are equally effective

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21
Q

How many highly emetogenic regimens exist for acute N/V?

A

3

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22
Q

What are the 4 types of drugs included in the acute N/V highly emetogenic regimen A?

A

NK-1 Antagonist (“tant”)
(Aprepitant, Fosaprepitant, Rolapitant, Netupitant/palonosetron, Fosnetupitant/palonosetron)

Steroid
(Dexamethasone)

5-HT3 Antagonist (“setron”)
(Dolasetron, Granisetron, Ondansetron, Palonosetron)

Atypical Antipsychotic
(Olanzapine)

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23
Q

What are the 3 types of drugs included in the acute N/V highly emetogenic regimen B?

A

Atypical Antipsychotic
(Olanzapine)

Steroid
(Dexamethasone)

5-HT3 Antagonist
(Palonosetron)

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24
Q

What are the 3 types of drugs included in the acute N/V highly emetogenic regimen C?

A

NK-1 antagonist
(“tant”)

Steroid
(Dexamethasone)

5-HT3 Antagonist
(“setron”)

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25
What three drugs can be added to any regimen at any emetogenicity if the patient is experiencing toxicities that might warrant a benzodiazepine or PPI?
Lorazepam H2 Blocker (Pepcid/famotidine, calcium carbonate) PPI (omeprazole, esomeprazole, pantoprazole)
26
For the moderately emetogenic regimen a, what are the 2 types of agents that should be used?
Steroid (dexamethasone) 5-HT3 Antagonist (dolasetron, granisetron, ondansetron, palonosetron)
27
For the low emetogenic regimen, what are the agents that you can pick from? (Pick 1)
Dexamethasone Metoclopramide Prochlorperazine 5-HT3 antagonists (Dolasetron, Granisetron, Ondansetron)
28
Treatment for delayed nausea/vomiting typically involves the use of one of which 3 agents?
Dexamethasone NK-1 Antagonist Olanzapine
29
Which drug can be used for treatment of anticipatory nausea and vomiting?
Lorazepam
30
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy Continue daily (5-HT3 antagonists)
31
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy May be given daily or prn
32
What is the treatment for radiation induced emesis?
Granisetron PO +/- dexamethasone Ondansetron PO +/- dexamethasone (5HT3 inhib + Steroid)
33
For which radiopharmaceutical is nausea associated with the amino acid infusion that accompanies treatment?
Lutetium Lu-177 dotatate
34
What are the common side effects associated with the 5HT3 Inhibitors? (trons)
Headache Constipation QTc prolongation *note: if side effects occur you CAN switch to another agent in the same class, not a class effect
35
What are the common side effects associated with dexamethasone? (corticosteroid)
Hyperglycemia Weight Gain (increased appetite)
36
What are the common side effects of Substance P Antagonists? (NK-1 antagonists) (tants)
Hiccups
37
What are the common side effects of the Dopamine Antagonists? (chlorpromazine, haloperidol, metoclopramide)
Extrapyramidal side effects Diarrhea
38
What are the common side effects of olanzapine?
sedation
39
What are the common side effects of phenothiazines? (prochlorperazine, promethazine)
Sedation
40
What are the common side effects of the cannibanoids? (dronabinol)
Drowsiness Weight Gain (increased appetite)
41
What are the side effects of lorazepam?
Sedation
42
What side effects are associated with the scopolamine patch?
Anticholinergic Side Effects (can't see, pee, shit, spit) **Note: older people do not do well on this, primarily for use in young people
43
When are antiemetics most effective?
When given as prophylaxis (5 to 30 mins before chemotherapy) -Administer around-the-clock until chemotherapy is complete and provide prn agents for breakthrough
44
True or False: Mucositis is only in the mouth
False -it can affect the entire GI tract all the way down to the colon
45
What is mucositis?
Ranges from mild inflammation to bleeding ulcers -GI mucosa is comprised of epithelial cells and has a rapid turnover rate
46
What are the steps of progression for mucositis?
*Parallels the neutrophil nadir* -Begins on day 5-7 after chemotherapy -Improves as the neutrophil count increases
47
What are 2 chemotherapies to remember that cause mucositis?
5-FU Anthrocycline
48
What are the 3 risk factors for mucositis?
Pre-existing oral lesions Poor dental hygiene or poor fitting dentures Combined chemo+radiation therapy
49
What are 3 dietary prevention methods to prevent mucositis development?
Avoid rough food, spices, salt, and acidic foods Eat soft food or liquid food Avoid smoking and alcohol
50
What are 3 mouthcare strategies for mucositis?
Baking soda rinses Soft-bristled toothbrush Saliva substitute (for radiation-induced xerostomia where the salivary glands are killed off)
51
What pain management strategies can be used for mucositis?
Topical anesthetics + Magic mouthwash (lidocaine, diphenhydramine, and antacid combos) Oral cryotherapy Sucralfate (swish and swallow, forms a protective barrier, can induce nausea) Oral or IV opioids (for moderate to severe cases) **PCA**
52
How does oral cryotherapy reduce the risk for mucositis?
Causes vasoconstriction which may lower the amount of chemotherapy delivered to the oropharyngeal mucosa
53
What is the only way to get rid of mucositis?
Increase white blood cell counts
54
What white blood cell count is indicative of severe neutropenia?
<0.5 x 10^3/uL
55
What is the most common dose-limiting toxicity of chemotherapy?
Bone marrow suppression/ Neutropenia
56
What is the nadir?
The lowest value that the blood counts fall to during a cycle of chemotherapy -Usually described by the absolute neutrophil count -Generally occurs 10-14 days after chemo -Counts normally recover by 3-4 weeks after chemo
57
How do we calculate Absolute Neutrophil Count (ANC)?
WBC x % Granulocytes
58
What are the typical guidelines used to assess if chemotherapy is safe to administer based on blood counts?
WBC > 3 ANC > 1.5 Platelet count > or = 100
59
True or False: Neutropenic patients are at an increased risk of developing infections
True
60
What values define febrile neutropenia?
ANC < 0.5 Single oral temperature >101F or >/= 100.4F for at least an hour **Get to hospital with this**
61
Why is it so important for a patient to go to the hospital if they experience neutropenic fever?
The usual signs of infection (abscess, pus, and infiltrates on a chest x-ray) are not present because of the low levels of white blood cells Fever is the only reliable indicator of infection
62
What can we use to increase WBC counts when they are low?
Colony Stimulating Factors (CSF's)
63
What patients should receive primary prophylaxis for neutropenia?
-If they receive a chemo regimen expected to cause >/= 20% incidence of febrile neutropenia -If they are high risk: --Have preexisting neutropenia due to disease --Extensive prior chemotherapy --Previous irradiation to pelvis or other areas with large amounts of bone marrow
64
What patients should receive secondary prophylaxis for neutropenia?
-Patient experienced a neutropenic complication from a previous cycle of chemo and now you want to prevent it from happening again
65
What 3 CSF's can be used to treat neutropenia?
Filgrastim Pegfilgrastim Sargramostim
66
Which has the longer half-life: Filgrastim or Pegfilgrastim?
Pegfilgrastim -more expensive -1 time injection
67
Which medication used for treatment of neutropenia gets cleared more quickly as neutrophil counts increase?
Pegfilgrastim
68
Which form of filgrastim is not considered a biosimilar?
Tbo-Filgrastim (Granix)
69
Which form of filgrastim was the first approved biosimilar?
Filgrastim-sndz (Zarxio)
70
Which drug used for treatment of neutropenia is available as the Onpro kit? (on-body self-injector kit that injects a dose of medication 24 hours after chemotherapy is received and prevents patient from coming having to come back to the hospital)
Pegfilgrastim (note that this acts as a one-time injection)
71
When do we start filgrastim and how long is it continued?
Start 3-4 days after completion of chemo Continue until post-nadir ANC recovers to normal or near normal
72
When do we start pegfilgrastim and how long is it continued?
Start at least 24 hours after chemo Can be given up to 3-4 days after chemo (at least 14 days should elapse between the dose and the next cycle of chemo) OnPro body injector can be applied the same day as chemo
73
What are the common adverse effects of CSF's?
Flu-like symptoms *Bone + Joint Pain DVT
74
What drug can be used to help with the side effects of CSF's?
Loratadine -because pain is thought to be due to histamine release
75
What is thrombocytopenia?
A platelet count < 100
76
At what platelet count should a transfusion be considered?
77
What patients should undergo a work-up for anemia?
Hgb /= 2 g/dL drop from baseline -want to determine cause
78
If a patient is experiencing symptomatic anemia, what are the 3 options for treatment?
Transfuse as indicated Erythropoietic Stimulating Agents (ESA) Perform Iron Study (need adequate iron for drugs to work)
79
What drug class has a black box warning for use in cancer patients and what is the warning?
Erythropoietin Stimulating Agents (ESA's) -cause shortened overall survival and/or increased risk of tumor progression *note: use the lowest doses possible of these agents *these are not used as commonly as they used to be
80
Who should ESA's not be used in?
Patients receiving myelosuppressive chemotherapy with curative intent Patients not receiving chemotherapy Patients receiving non-myelosuppressive chemotherapy
81
Who should ESA's be considered in?
Cancer and chronic kidney disease Patients undergoing palliative chemo Patients without other identifiable causes
82
What are the 2 commonly used ESA's for chemotherapy-associated anemia?
Epoetin alfa (erythropoietin) Darbapoetin (Aranesp)
83
When should we decrease the doses of epoetin alpha and darbepoetin during treatment of anemia?
If the Hgb increases > 1g/dL in a 2-week period -Decrease epoetin dose by 25% -Decrease darbepoetin dose by 40%
84
What patients should have baseline iron studies performed?
All patients prescribed ESA therapy
85
What are the 3 iron products that can be given to patients?
Low Molecular Weight Iron Dextran (Dexferrum) Iron Sucrose (Venofer) Ferric Gluconate (Ferrlecit)
86
Mesna should be used with doses of what chemotherapy?
Isofosfamide
87
Mesna is used to prevent what?
Hemorrhagic cystitis
88
How does cardiac toxicity occur?
Iron-dependent oxygen free radicals form -Cause catalysis of electron transfer -The myocardium is susceptible because it has lower levels of enzymes capable of detoxifying oxygen free radicals compared to other tissues
89
Which chemotherapy agents are most likely to cause Type 1 cardiac dysfunction?
Anthracyclines (doxorubicin)
90
Which chemotherapy agent is most likely to cause Type 2 cardiac dysfunction?
Trastuzumab *not dose related *not associated with cardiac damage (reversible) -Involves the EGFR pathway (can restart therapy once EGFR goes back to normal) Note: risk increases when used with anthracyclines, do not use these together
91
What are the assessment questions for pain?
OPQRSTU -What is the onset? -What provokes the pain? -What is the quality of pain? -Does the pain radiate? -How severe is the pain? -Time of pain? -Understanding and Impact (what is the patient's understanding of their pain and what is their goal)
92
What patient factors should we consider when determining appropriate analgesic therapy?
-Pain severity -Medication access (price) -Hepatic/renal function -Previous analgesic therapy (did it work?)
93
What should Step 1 pain therapy consist of (mildest pain)(1-3 rating)?
Non-opioid Adjuvant
94
What should Step 2 pain therapy consist of (moderate pain)(4-6 rating)?
Opioid for mild to moderate pain Non-opioid Adjuvant
95
What should Step 3 pain therapy consist of (most severe pain)(7-10 rating)?
Opioid for moderate to severe pain Non-opioid Adjuvant
96
When should morphine not be used?
Renal dysfunction! -metabolites are excreted renally and will build up in renal failure *use caution in liver dysfunction
97
Can hydromorphone be used in renal and hepatic dysfunction?
Yes but: -Has renally excreted metabolites, lower dose or use longer dosing intervals in renal insufficiency -Use caution in liver dysfunction
98
What is oxycodone metabolized by?
CYP2D6
99
Can oxycodone be used in renal and hepatic dysfunction?
Use caution in both -Over sedation and CNS toxicity have been reported in renal failure patients
100
What formulation does oxycodone NOT come in?
No IV formulations
101
What opioid is the safest to use in renal dysfunction?
Fentanyl *metabolized in the liver but is safe in dysfunction*
102
Besides renal dysfunction, Fentanyl also acts as a great alternative in which patients?
Refractory nausea/vomiting Head/neck/esophageal cancer patients unable to maintain adequate PO intake
103
What is the REMS warning on fentanyl for?
Transmucosal and Nasal Preparations -Risk of addiction, abuse, and misuse -Respiratory depression -Accidental exposure from improper disposal -Avoid having the patch on a direct external heat source as this increases vasodilation, increases uptake, and can lead to overdose
104
Who should not receive fentanyl?
Opioid naive patients
105
Who should methadone be considered in?
Patients with: -True morphine allergy -Opioid-induced adverse drug reaction -Refractory pain with other high dose opioids -Neuropathic pain -Who need long-acting po form at low cost
106
Who should not receive methadone?
Patients with: -Numerous drug interactions -Risks for syncope or arrythmia -History of non-adherence -Poor cognition
107
Can methadone be used in renal dysfunction?
Can be used in renal failure (no reported adverse effects) BUT DO NOT USE IN SEVERE LIVER FAILURE -QT prolongation
108
When switching between opioid agents, how much should we dose reduce by?
25% due to cross tolerance
109
What side effect in opioids do patients not develop tolerance to?
Constipation
110
Who can receive a Patient Controlled Analgesia (PCA) pump?
Only patients who are awake, oriented, and able to self-administer their doses
111
How do we calculate a patients total opioid usage with a PCA?
24-hour dose: Basal rate + Number of hits used daily
112
How do we decide what breakthrough (prn) dosing of opioids should be?
10-20% of patient's total 24-hour oral dose available every 4 hours prn (more often if IV)
113
What is the celiac plexus?
A group of nerves that supply organs in the abdomen
113
Who is a celiac plexus block mostly used in?
Patients with pancreatic cancer (due to involvement of celiac plexus)
114
Who can recieve an intrathecal pain pump?
Patients who are refractory to other opioid therapies or have increased toxicities -patients who are not obtaining relief with opioid therapy and are reaching levels of toxicity
115
What is the conversion factor of oral morphine to intrathecal morphine?
300:1 *note that intrathecal morphine is extremely potent
116
In what scenarios is radiation therapy used to relieve pain?
Bony metastases Brain metastases Spinal cord compression
117
What agents should be considered for neuropathic pain?
Gabapentin Pregabalin Duloxetine
118
Using the RECIST criteria, what is a complete response (CR)?
Disappearance of all target lesions
119
Using the RECIST criteria, what is a partial response (PR)?
30% decrease in the sum of the longest diameter of target lesions
120
Using the RECIST criteria, what is progressive disease (PD)?
20% increase in the sum of the longest diameter of target lesions
121
Using the RECIST criteria, what is stable disease (SD)?
Small changes that do not meet other criteria
122
What is the #1 cancer in females and second most cause of death of all cancers in the US?
Breast cancer
123
What % of patients will not have any risk factors for breast cancer but still develop it?
60%
124
What % of breast cancers are familial?
5-10%
125
What are the 2 tumor suppressor genes in breast cancer?
BRCA-1 BRCA-2
126
What is the GAIL risk model?
Mathematical risk assessment tool used to determine the relative risk in % of developing breast cancer compared to an age-matched control at 5 years and during one's lifetime
127
What are the 2 types of invasive breast cancer carcinoma?
Invasive ductal carcinoma (IDC) *most common Invasive lobular carcinoma (ILC) *note that these have invaded beyond the basement membrane of the duct or lobule
128
What is the most common type of breast cancer that accounts for 70% of all breast cancers?
Invasive ductal carcinoma (IDC)
129
What are the 2 types of non-invasive breast cancer?
Ductal carcinoma in situ (DCIS) --normal cells have undergone pre-malignant transformation Lobular carcinoma in situ (LCIS) --has not yet invaded beyond the lobule basement membrane
130
What is inflammatory breast cancer?
-Aggressive form with a rapid onset and poor prognosis -Onset is days or weeks Symptoms: edema, redness, warmth, inflammation, peau d'orange
131
What is FISH testing?
Testing for HER2 status done in two ways: -Immunohistochemistry: Detects protein overexpression (0=neg, 1+=low, 2+=do FISH test, 3+=high use HER2 therapy) -Fluorescence In-Situ Hybridization (FISH): detects gene amplification ( if gene:chromosome copies are >/=2 it is positive)
132
What is Oncotype DX?
Genetic test for expression of 21 genes which gives a recurrence score (predicts recurrence risk and whether the patient is likely to benefit from chemo)
133
What is a low risk Oncotype DX score and how does this affect the therapy we choose for breast cancer?
Low risk is <26 *Hormone therapy only
134
What is a high risk Oncotype DX score and how does this affect the therapy we choose for breast cancer?
High risk is >26 *Use both chemotherapy and hormone therapy
135
What group of people still incur benefits from chemotherapy even though they have a low Oncotype DX score?
Women <50 years of age with a score of 16-25 *use chemotherapy in these women
136
What is an adjuvant?
Treatment given after surgery
137
What is a neoadjuvant?
Treatment given before surgery
138
For what stages of breast cancer is the goal to cure the patient?
1-3 Stage 4 is palliative care
139
Which breast cancer patients should receive neoadjuvant therapy?
Patients with tumors > 1cm
140
What are the benefits of neoadjuvant therapy?
Allows for less extensive surgery by shrinking the tumor Allows you to see the tumor's response to chemo while it is still intact
141
For tumors
Adjuvant endocrine therapy
142
For tumors > 0.5cm or 1-3 positive nodes, what adjuvant therapy should be used? (Hormone+, Lymph node +/-, HER2-)
First: Complete a 21 gene RT-PCR assay If not done: Endocrine therapy or chemo followed by endocrine therapy RS<26: Endocrine therapy RS>/= 26: Chemo followed by endocrine therapy *give chemo in younger women
143
What adjuvant therapy should women with breast cancer receive if: Hormone+, Lymph Node+/-, and HER2+
Tumor 0.6cm: Chemo with HER2 targeted therapy followed by endocrine therapy
144
What hormonal adjuvant therapy should pre-menopausal women receive that post-menopausal women do not need?
Oopherectomy -remove the ovaries which is the largest producer of estrogen (estrogen drives these tumors)
145
How long does adjuvant therapy in breast cancer typically last?
5 years, then reassess and determine if 5 more years are needed
146
How many cycles of chemotherapy are typically used in breast cancer treatment and how often are they given?
4-6 cycles of chemotherapy given every 3-4 weeks
147
How many cycles of chemotherapy does neoadjuvant treatment in breast cancer typically consist of?
4-6 cycles
148
When deciding on a breast cancer chemotherapy regimen, what is the most important factor to keep in mind?
Cardiac risks (do not use anthracyclines in patients with these risks)
149
If a breast cancer patient has cardiac problems, what chemotherapies can we consider using?
Docetaxel Cyclophosphamides (TC) *avoid anthracyclines
150
What HER2 targeted therapy can be added on to a breast cancer patient's chemo regimen for HER2+ disease?
Trastuzumab Pertuzumab
151
How long should HER2 targeted therapy (Trastuzumab and Pertuzumab) be continued in breast cancer treatment?
1 year
152
What treatment should be added to the chemotherapy regimen for patients with Triple Negative Breast Cancer?
Immunotherapy (pembrolizumab)
153
Who may be better to receive hormonal therapy in metastatic breast cancer?
-Long drug free period with prior therapy -Assess menopausal status **ER+/PR+ -Prior response to therapy -Bone only disease
154
Who may be better to receive chemotherapy in metastatic breast cancer?
-Short disease-free period -Rapidly progressing disease -Disease refractive to hormonal therapy **ER-/PR- disease -Better performance status patients
155
True or False: Combination chemotherapy in metastatic breast cancer patients has not been shown to be more effective
True
156
Which regimen in metastatic breast cancer is used only for HER2 low patients (1+)?
Fam-trastuzumab Deruxtecan
157
What are the CDK 4/6 inhibitors?
Abemaciclib Palbociclib Ribociclib
158
What are the common side effects of the CDK4/6 inhibitors?
Abemaciclib: Diarrea Palbociclib: Ribociclib: QTc Prolongation (need to check EKG) ***all need a complete blood count (CBC) to be done *Check these drugs monthly
159
At what age can you start having mammograms?
40
160
At what age should you start having annual mammograms?
45
161
What is the most common type of cancer in men?
Prostate cancer
162
Prostate cancer is driven by what?
Testosterone (growth signal to the prostate) Alterations in the androgen receptor
163
What are the risk factors for prostate cancer?
Older age (increased lifetime exposure to testosterone) Race (African Americans have higher risk, Asians have lower risk) Family history
164
What are the methods used to diagnose prostate cancer?
Physical exam PSA level Biopsy of prostate Transrectal ultrasound
164
Where are the most common places that prostate cancer will metastasize to?
Bone Lung Liver
165
What is the most common histology of prostate cancer?
Adenocarcinoma (99%)
166
What is the Gleason score and what does it mean?
Score to rank prostate cancers -Scores assigned to primary and secondary growth patterns, then added together Score of 2-4: slow-growing, well differentiated Score 8-10: aggressive, poorly differentiated *Lowest= 1+1=2 *Highest= 5+5=10 Note: the higher the score, the higher the risk of extracapsular spread
167
What is the normal Prostate Specific Antigen (PSA) range?
0-4
168
What PSA level requires evaluation?
>4
169
What PSA level is highly suspicious for malignancy?
>10
170
What PSA velocity is suspicious for malignancy?
>0.75 rise per year
171
What does m1 mean in prostate cancer?
metastatic
172
What does m0 mean in prostate cancer?
non-metastatic (only thing that is off is that the PSA is increasing)
173
What is HSPC?
Hormone sensitive prostate cancer
174
What is CRPC?
Castration resistant prostate cancer
175
What is the treatment for localized prostate cancer?
Monitoring! -Active surveillance (if it progresses, initiate potentially curative therapy) -Expectation to deliver palliative therapy for symptom development, change in exam, or PSA suggesting symptoms are coming -If cancer progresses, use radiation therapy or surgery
176
What are the 2 types of radiation therapy that can be used in localized prostate cancer?
External beam Brachy therapy (implanted pellets around prostate)
177
If a patient with progressed localized prostate cancer is immediate or low risk, what adjuvant can we add onto their regimen?
Androgen deprivation therapy (ADT)
178
For locally advanced/high risk prostate cancer, what treatment has been shown to be effective?
Androgen deprivation therapy with External beam radiation therapy
179
When Androgen deprivation therapy (ADT) and external beam radiation therapy are used together, how should they be dosed?
Start ADT prior to radiation Continue ADT during radiation therapy and for 1-3 years after
180
For localized prostate cancer, what is the definitive curative therapy?
Radical Prostatectomy (prostate removal) + Pelvic lymph node dissection (PLND)
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What is the goal of androgen deprivation therapy?
Induce castration levels of testosterone
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What drugs/drug class are considered Androgen Deprivation Therapy?
LHRH agonists -Leuprolide -Goserelin
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True or False: LHRH agonists (leuprolide and goserelin) cause reversible castration in males with prostate cancer
True
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What is the main toxicity associated with LHRH agonists?
Tumor flares (elevate hormones until receptors eventually shut down and cause castration)
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What drug can be used instead of LHRH agonists in patients with cardiac history or need an oral drug?
Relugolix
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What are the anti-androgen drugs?
Flutamide Bicalutamide***** Nilutamide
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When are anti-androgens (flutamide, bicalutamide, nilutamide) used in prostate cancer?
Metastatic setting -given in combination with LHRH agonists and used to prevent the hormone flare that these can cause
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What are the 3 principles that should be considered in metastatic prostate cancer?
1. Goal is palliation of disease and to suppress testosterone production 2. Determine whether this is a PSA recurrence or overt metastatic disease 3. Determine PSA doubling time
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Which prostate cancer patients can consider using intermittent ADT therapy?
Men with biochemical failure only
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When metastatic prostate cancer is not responding to ADT and the PSA is increasing, what drugs can we add?
Enzalutamide Apalutamide (not for m0 group) Darolutamide
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What is the moa of enzalutamide?
Blocks androgen binding and translocation of androgen receptor
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Who should enzalutamide be used with caution in?
Patients with seizure history
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What is the moa of apalutamide?
Non-steroidal androgen receptor inhibitor
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Which drug in prostate cancer is metabolized by CYP3A4?
Darolutamide
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What is m1HSPC?
Prostate cancer that now has visceral metastases and is hormone sensitive -determine therapy based on high or low volume
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What is the treatment for low volume m1HSPC?
ADT: LHRH agonist or antagonists Continue ADT and add one of the following: -Abiraterone+Prednisone -Enzalutamide -Apalutamide
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Which drug must be given with prednisone and why?
Abiraterone -because it causes adrenal insufficiency (prednisone blocks this)
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What is the moa of abiraterone?
Inhibits CYP17 which is an enzyme required for androgen synthesis -inhibits testosterone precursor formation
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What is the 1st line therapy for High Volume m1HSPC?
Docetaxel+ ADT can also use: ADT+Docetaxel+Abiraterone (+prednisone) ADT+Docetaxel+Darolutamide
200
When do we consider using chemotherapy in prostate cancer treatment?
High Volume m1HSPC
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What is the second-line chemotherapy that can be used in high volume metastatic prostate cancer?
Cabazitaxel
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What drug can be used in prostate cancer tumors that express dMMR or MSI-H?
Pembrolizumab
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How is goserelin administered?
Subq implant
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How is leuprolide administered?
Subq or IM injection
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At what age should men start screening for prostate cancer?
50
206
What PSA level indicated the need for annual screenings?
PSA>/= 2.5
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WHat PSA level indicates the need for screening every 2 years?
PSA<2.5
208
EGFR mutations in lung cancer predict sensitivity to what?
Tyrosine kinase inhibitor (TKI) therapy
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K-RAS mutations in lung cancer predict resistance to what?
Predict resistance to Tyrosine kinase inhibitors (TKI)
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What 2 mutations in lung cancer may appear in individuals who have never smoked/are light smokers?
ALK inhibition (anaplastic lymphoma kinase) ROS-1 mutations *also typically do not have PD-1 expression (this does not affect outcomes)
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Which form of lung cancer has a clear relationship to smoking?
Small cell lung cancer
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Which form of lung cancer has rapid cell growth?
Small cell lung cancer (this type of cancer responds well to chemo)
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Which form of lung cancer has slow growth?
Non-small cell lung cancer (moderate sensitivity to chemo and radiation)
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What is limited stage lung cancer?
Tumor is confined to hemithorax and contained in a radiation port, no distant metastases -Only 30% of patients have this
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What is extensive stage lung cancer?
Tumor is not confined to hemithorax, not contained in a radiation port, and has distant metastases -70% of patients have this
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For small cell lung cancer limited stage disease, what is the treatment?
Radiation + Chemo combined Cisplatin + Etoposide (platinum doublet) 4-6 cycles Radiation daily (M-F) for 6-7 weeks
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Which form of lung cancer has a high risk of brain metastases?
Small Cell Lung Cancer
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What is the treatment for small cell lung cancer extensive stage disease?
Platinum doublet chemo + Immunotherapy Cisplatin + Etoposide +Atezolizumab/Durvalumab
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What are the side effects of cisplatin?
Nausea/vomiting Nephrotoxicity Ototoxicity (do not use in patients with hearing loss) Neuropathy
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What drug can be used in patients with metastatic SCLC who have progressed on platinum-based therapy?
Pembrolizumab
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What is the neoadjuvant regimen for resectable NSCLC?
Nivolumab + Platinum doublet (Cisplatin+Etoposide)
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What is the adjuvant chemotherapy regimen for resectable NSCLC?
Non-squamous: Cisplatin + Pemetrexed Squamous: Cisplatin + Gemcitabine, Cisplatin + Docetaxel
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If a lung cancer patient has a targetable mutation and is PD-L1+ what therapies are preferred to use first?
Oral therapies (then move to immunotherapy later)
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What targeted therapy should be used in lung cancer patients with EGFR mutations (Exon 19 deletion, Exon 21 L858R mutation?
Osimertinib
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What targeted therapy should be used in lung cancer patients with BRAF mutations?
Dabrafenib + Trametinib (BRAF inhibitor + MEK inhibitor) -BRAF inhibitors can cause skin cancer, this is prevented by the MEK inhibitor
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What drug should be added on as subsequent therapy in patients with a K-RAS G12C mutation?
Sotorasib
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In patients with PD-L1 positivity >/= 1% what treatment do we use?
Pembrolizumab
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All mutation negative, non-squamous, NSCLC patients should receive what therapy?
Carboplatin + Pemetrexed + Pembrolizumab
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What is the treatment for squamous NSCLC?
Pembrolizumab + Carboplatin + Paclitaxel
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Who should be screened for lung cancer?
High risk patients Age 55--74 30-year history of smoking and still smoking or quit in last 15 years In good health *Willing to have curative surgery if detected
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What is the clinical presentation of skin lesions? (remember ABCDE)
Asymmetric irregular Borders variety of Colors Diameter >6mm Evolution of a mole may indicate cancer
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If a melanoma is a clinical stage IV, it should be tested for what?
BRAF V600E and K mutations
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What is Moh's surgery?
Used for melanoma removal -take paper thin slices of tissue, keep looking under the microscope until there is no evidence of disease
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What did the checkmate 238 trial do?
Compared nivolumab to ipilimumab in melanoma -found that toxicities were higher with ipilimumab *This made nivolumab a category 1 recommendation
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What did the KEYNOTE-054 trial do?
Pembrolizumab was compared to placebo in stage III melanoma -Pembrolizumab improved recurrence free survival and reduced risk of metastases
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What is the most common side effect of Dabrafenib + Trametinib?
Pyrexia (fevers)
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What did KEYNOTE-006 trial do?
Compared pembrolizumab with ipilimumab -pembrolizumab has less toxicity -pembrolizumab worked better
238
What are the ipilimumab toxicities in melanoma?
Since response is based on the patient's immune system's ability to kill the melanoma, some patients have tumor growth prior to immune system activation *all patients should receive all 4 doses unless they experience life threatening toxicity
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What age does screening for colorectal cancer start?
45
240
What 2 disease states increase the risk for development of colorectal cancer?
Ulcerative colitis Crohn's disease (inflammatory conditions of the GI tract)
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What hereditary syndromes increase the risk for colorectal cancer?
Familial Adenomatous Polyposis (FAP) -development of 100's to 1000's adenomatous polyps -Nearly 100% lifetime risk of developing colon cancer *undergo colectomy when polyps appear Hereditary Nonpolyposis Colorectal Cancer (HNPCC)
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What age does screening for colorectal start for patients with Familial Adenomatous Polyposis (FAP)?
10-12 years old
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>95% of colorectal cancers have what origin?
Adenocarcinomas (glands)
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What does Defective DNA mismatch repair (dMMR) test for? (in colorectal cancer)
Microsatellite instability (MSI) or Loss of genes involved in DNA mismatch repair (MMR)
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dMMR or MSI-H tumors in colorectal cancer predict what?
Decreased benefit from adjuvant 5-FU therapy for Stage II disease *note: Stage III disease still benefits
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What drugs are included in FOLFOX?
5-Flurouracil Leucovorin Oxaliplatin
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What drugs are included in CapeOX?
Capecitabine Oxaliplatin
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What did the MOSAIC trial show?
FOLFOX significantly increased 6-year survival in colorectal cancer patients
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What did the IDEA trial test?
Evaluated if 3 months of oxiplatin therapy (FOLFOX and CapeOx) was non-inferior to 6 months of oxiplatin therapy (FOLFOX and CapeOx) Results: Longer time resulted in more toxicity (neuropathy) and lower adherence CapeOx: 3 months was equally effective as 6 months FOLFOX: 6 months was MORE effective
250
How does administration of FOLFOX differ from CapeOx?
FOLFOX: port, 2-day continuous pump at home, repeat every 2 weeks CapeOx: PO for 14 days then off for 7
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If a patient with colorectal cancer has neuropathy, what drug may not be a good option for them?
Oxaloplatin
252
If a patient with colorectal cancer has a UGT1A1 deficiency, what drug needs to have its dose changed?
Irinotecan
253
KRAS mutations predict lack of response to which drugs?
anti-EGFR monoclonal antibodies (do not use cetuximab or panitumumab)
254
Which two screening tests are used to detect colorectal cancer?
Fecal occult blood test (FOBT) -high false negative rate Fecal immunohistochemical test (FIT)
255
Which tests are used to detect colorectal cancer and advanced lesions?
Endoscopy (Colonoscopy) Radiological exams
256
At what age should patients start being screened for colon cancer?
45
257
How often should a colonoscopy be done?
Every 10 years
258
If a patient has a family history of a 1st degree relative with colon cancer, when should they start screening?
Age 40 OR: 10 years younger than the youngest age of diagnosis in the family
259
What treatments are available to prevent colon cancer?
Cyclooxygenase inhibitors (celecoxib) NSAIDs or Aspirin Colectomy (if family history)
260
What is a proposed cause of ovarian cancer?
"Incessant ovulation" theory -risk of developing ovarian cancer is related to her number of ovulatory cycles because each ovulation results in disruption and repair of epithelial lining in the ovaries
261
What genetic mutations increase the likelihood of getting ovarian cancer?
BRCA 1 BRCA 2 p53
262
What is Lynch II syndrome?
Hereditary nonpolyposis colorectal cancer -Familial predisposition to colon cancer, endometrial cancer, and ovarian cancer
263
True or False: Most patients with Stage I and Stage II ovarian cancer are asymptomatic
True *most patients present with advanced disease
264
When should a woman seek medical attention regarding ovarian cancer symptoms?
If she experiences symptoms for 12 or more days out of a month for 2 consecutive months
265
How does ovarian cancer progress?
Starts in ovary and spreads throughout the peritoneal cavity (abdominal cavity)
266
True or False: Ovarian cancer responds well to chemo
True! -but most patients will experience reoccurrence within the first 3 years
267
After a patient receives surgery for ovarian cancer they are split into two groups, what patients are considered "optimally debulked"?
<1 cm of disease remaining
268
After a patient receives surgery for ovarian cancer they are split into two groups, what patients are considered "sub-optimally debulked"?
> 1 cm of disease remaining
269
What is the standard chemotherapy regimen used in ovarian cancer?
Paclitaxel + Carboplatin every 3 weeks for 6 cycles
270
When taking carboplatin, what causes a Type I reaction to develop?
Drug/antigen specific IgE's that have high binding affinity to receptors on mast cells and basophils -receptor cross-linking triggers histamine and inflammatory mediators release
271
When taking carboplatin, what causes a Type IV reaction to develop?
-Delayed hypersensitivity reaction -Occurs when antigen sensitized cells release cytokines after subsequent contact
272
How many cycles of carboplatin result in an increased risk of developing a Type IV hypersensitivity reaction?
>/= 8 cycles (this is considered repeat exposure)
273
Can you give a patient paclitaxel again if they have had a hypersensitivity reaction?
YES -use small dilutions and slowly ramp up (*note: can also do this with carboplatin)
274
What is the biggest side effect associated with PARP inhibitors? (olaparib, niraparib, rucaparib)
Anemia
275
What does it mean for an ovarian cancer patient to be "platinum sensitive"?
They relapse > 6 months after completion of their initial platinum containing regimen **Can be treated with original regimen again
276
What does it mean for an ovarian cancer patient to be "platinum resistant"?
They relapse < 6 months after completion of their initial platinum containing regimen **Now should be treated with a salvage regimen
277
What does it mean for an ovarian cancer patient to be "platinum progressive"?
They have no response/ progression of disease while on the original platinum chemotherapy treatment
278
What is the first-line single agent used in patients who are platinum resistant?
Liposomal Doxorubicin
279
True or False: There are no effective screening tools for ovarian cancer
True
280
How do we diagnose skeletal related events?
Radionucleotide bone scan
281