Therapeutics Exam 2 (Supportive Care) Flashcards
What is the most feared complication of chemotherapy?
Chemotherapy Induced Nausea and Vomiting (CNV)
What are the 5 types of Nausea/Vomiting?
Anticipatory
Acute
Delayed
Breakthrough
Refractory
What is anticipatory nausea/vomiting?
-A learned response conditioned by previous emetic reactions from prior cycles of chemotherapy
-Can be provoked by sight, sound, or smell
What is acute nausea/vomiting?
-Emetic response that correlates with the administration of chemotherapy
within 24 hours of receiving chemotherapy
What is delayed nausea/vomiting?
-Related to chemotherapy but occurs >24 hours after completion
What is breakthrough nausea/vomiting?
Occurs even though the patient is on scheduled anti-emetics prior to chemotherapy
What is refractory nausea/vomiting?
Persists despite appropriate anti-emetic therapy
-Patient has failed other therapies at this point
How does chemotherapy cause CINV?
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
Which cells are responsible for the massive release of serotonin in the GI tract after chemotherapy that leads to CINV?
Enterochromaffin cells
Which neurotransmitter can be targeted to treat breakthrough CINV?
Dopamine
What are the 2 most commonly targeted neurotransmitters for treatment of CINV?
Serotonin
Substance P
Which receptor mediates the action of substance P?
neurokinin-1 receptor
Which chemotherapy produces the most nausea?
Cisplatin
How does the combination of chemotherapies affect emetogenicity?
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
Who is at a higher risk for CINV: Men or Women?
Women
Who is at a higher risk for CINV: Younger Patients or Older Patients
Younger Patients
What are 4 risk factors of CINV?
Prior history of motion sickness
Prior history of morning sickness
Previous CINV
Anxiety/high pretreatment anticipation of nausea
What trait can be protective against CINV?
Chronic ethanol use
How do we decide what prophylaxis to use for acute nausea and vomiting?
It is based on the emetogenic potential of the chemotherapy
Which is more efficacious: Oral or IV CINV prophylaxis
NEITHER, their are equally effective
How many highly emetogenic regimens exist for acute N/V?
3
What are the 4 types of drugs included in the acute N/V highly emetogenic regimen 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)
What are the 3 types of drugs included in the acute N/V highly emetogenic regimen B?
Atypical Antipsychotic
(Olanzapine)
Steroid
(Dexamethasone)
5-HT3 Antagonist
(Palonosetron)
What are the 3 types of drugs included in the acute N/V highly emetogenic regimen C?
NK-1 antagonist
(“tant”)
Steroid
(Dexamethasone)
5-HT3 Antagonist
(“setron”)
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)
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)
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)
Treatment for delayed nausea/vomiting typically involves the use of one of which 3 agents?
Dexamethasone
NK-1 Antagonist
Olanzapine
Which drug can be used for treatment of anticipatory nausea and vomiting?
Lorazepam
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy
Continue daily (5-HT3 antagonists)
When/how long should drugs be given for the highly/moderately emetogenic regimen?
Start before chemotherapy
May be given daily or prn
What is the treatment for radiation induced emesis?
Granisetron PO +/- dexamethasone
Ondansetron PO +/- dexamethasone
(5HT3 inhib + Steroid)
For which radiopharmaceutical is nausea associated with the amino acid infusion that accompanies treatment?
Lutetium Lu-177 dotatate
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
What are the common side effects associated with dexamethasone? (corticosteroid)
Hyperglycemia
Weight Gain (increased appetite)
What are the common side effects of Substance P Antagonists? (NK-1 antagonists) (tants)
Hiccups
What are the common side effects of the Dopamine Antagonists? (chlorpromazine, haloperidol, metoclopramide)
Extrapyramidal side effects
Diarrhea
What are the common side effects of olanzapine?
sedation
What are the common side effects of phenothiazines? (prochlorperazine, promethazine)
Sedation
What are the common side effects of the cannibanoids? (dronabinol)
Drowsiness
Weight Gain (increased appetite)
What are the side effects of lorazepam?
Sedation
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
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
True or False: Mucositis is only in the mouth
False
-it can affect the entire GI tract all the way down to the colon
What is mucositis?
Ranges from mild inflammation to bleeding ulcers
-GI mucosa is comprised of epithelial cells and has a rapid turnover rate
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
What are 2 chemotherapies to remember that cause mucositis?
5-FU
Anthrocycline
What are the 3 risk factors for mucositis?
Pre-existing oral lesions
Poor dental hygiene or poor fitting dentures
Combined chemo+radiation therapy
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
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)
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
How does oral cryotherapy reduce the risk for mucositis?
Causes vasoconstriction which may lower the amount of chemotherapy delivered to the oropharyngeal mucosa
What is the only way to get rid of mucositis?
Increase white blood cell counts
What white blood cell count is indicative of severe neutropenia?
<0.5 x 10^3/uL
What is the most common dose-limiting toxicity of chemotherapy?
Bone marrow suppression/ Neutropenia
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
How do we calculate Absolute Neutrophil Count (ANC)?
WBC x % Granulocytes
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
True or False: Neutropenic patients are at an increased risk of developing infections
True
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
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
What can we use to increase WBC counts when they are low?
Colony Stimulating Factors (CSF’s)
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
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
What 3 CSF’s can be used to treat neutropenia?
Filgrastim
Pegfilgrastim
Sargramostim
Which has the longer half-life: Filgrastim or Pegfilgrastim?
Pegfilgrastim
-more expensive
-1 time injection
Which medication used for treatment of neutropenia gets cleared more quickly as neutrophil counts increase?
Pegfilgrastim
Which form of filgrastim is not considered a biosimilar?
Tbo-Filgrastim (Granix)
Which form of filgrastim was the first approved biosimilar?
Filgrastim-sndz (Zarxio)
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)
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
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
What are the common adverse effects of CSF’s?
Flu-like symptoms
*Bone + Joint Pain
DVT
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
What is thrombocytopenia?
A platelet count < 100
At what platelet count should a transfusion be considered?
</=10
*may also be indicated at higher levels if the patient has active bleeding
What patients should undergo a work-up for anemia?
Hgb </= 11 g/dL OR >/= 2 g/dL drop from baseline
-want to determine cause
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)
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
Who should ESA’s not be used in?
Patients receiving myelosuppressive chemotherapy with curative intent
Patients not receiving chemotherapy
Patients receiving non-myelosuppressive chemotherapy
Who should ESA’s be considered in?
Cancer and chronic kidney disease
Patients undergoing palliative chemo
Patients without other identifiable causes
What are the 2 commonly used ESA’s for chemotherapy-associated anemia?
Epoetin alfa (erythropoietin)
Darbapoetin (Aranesp)
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%
What patients should have baseline iron studies performed?
All patients prescribed ESA therapy
What are the 3 iron products that can be given to patients?
Low Molecular Weight Iron Dextran (Dexferrum)
Iron Sucrose (Venofer)
Ferric Gluconate (Ferrlecit)
Mesna should be used with doses of what chemotherapy?
Isofosfamide
Mesna is used to prevent what?
Hemorrhagic cystitis
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
Which chemotherapy agents are most likely to cause Type 1 cardiac dysfunction?
Anthracyclines (doxorubicin)
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
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)
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?)
What should Step 1 pain therapy consist of (mildest pain)(1-3 rating)?
Non-opioid
Adjuvant
What should Step 2 pain therapy consist of (moderate pain)(4-6 rating)?
Opioid for mild to moderate pain
Non-opioid
Adjuvant
What should Step 3 pain therapy consist of (most severe pain)(7-10 rating)?
Opioid for moderate to severe pain
Non-opioid
Adjuvant
When should morphine not be used?
Renal dysfunction!
-metabolites are excreted renally and will build up in renal failure
*use caution in liver dysfunction
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
What is oxycodone metabolized by?
CYP2D6
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
What formulation does oxycodone NOT come in?
No IV formulations
What opioid is the safest to use in renal dysfunction?
Fentanyl
metabolized in the liver but is safe in dysfunction
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
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
Who should not receive fentanyl?
Opioid naive patients
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
Who should not receive methadone?
Patients with:
-Numerous drug interactions
-Risks for syncope or arrythmia
-History of non-adherence
-Poor cognition
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
When switching between opioid agents, how much should we dose reduce by?
25% due to cross tolerance
What side effect in opioids do patients not develop tolerance to?
Constipation
Who can receive a Patient Controlled Analgesia (PCA) pump?
Only patients who are awake, oriented, and able to self-administer their doses
How do we calculate a patients total opioid usage with a PCA?
24-hour dose: Basal rate + Number of hits used daily
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)
What is the celiac plexus?
A group of nerves that supply organs in the abdomen
Who is a celiac plexus block mostly used in?
Patients with pancreatic cancer
(due to involvement of celiac plexus)
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
What is the conversion factor of oral morphine to intrathecal morphine?
300:1
*note that intrathecal morphine is extremely potent
In what scenarios is radiation therapy used to relieve pain?
Bony metastases
Brain metastases
Spinal cord compression
What agents should be considered for neuropathic pain?
Gabapentin
Pregabalin
Duloxetine
Using the RECIST criteria, what is a complete response (CR)?
Disappearance of all target lesions
Using the RECIST criteria, what is a partial response (PR)?
30% decrease in the sum of the longest diameter of target lesions
Using the RECIST criteria, what is progressive disease (PD)?
20% increase in the sum of the longest diameter of target lesions
Using the RECIST criteria, what is stable disease (SD)?
Small changes that do not meet other criteria
What is the #1 cancer in females and second most cause of death of all cancers in the US?
Breast cancer
What % of patients will not have any risk factors for breast cancer but still develop it?
60%
What % of breast cancers are familial?
5-10%
What are the 2 tumor suppressor genes in breast cancer?
BRCA-1
BRCA-2
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
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
What is the most common type of breast cancer that accounts for 70% of all breast cancers?
Invasive ductal carcinoma (IDC)
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
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
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)
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)
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
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
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
What is an adjuvant?
Treatment given after surgery
What is a neoadjuvant?
Treatment given before surgery
For what stages of breast cancer is the goal to cure the patient?
1-3
Stage 4 is palliative care
Which breast cancer patients should receive neoadjuvant therapy?
Patients with tumors > 1cm
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
For tumors </= 0.5 cm what adjuvant therapy should be used?
Adjuvant endocrine therapy
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
What adjuvant therapy should women with breast cancer receive if:
Hormone+, Lymph Node+/-, and HER2+
Tumor </= 0.5cm: endocrine therapy +/- chemotherapy with HER2 targeted therapy
Tumor >0.6cm: Chemo with HER2 targeted therapy followed by endocrine therapy
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)
How long does adjuvant therapy in breast cancer typically last?
5 years, then reassess and determine if 5 more years are needed
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
How many cycles of chemotherapy does neoadjuvant treatment in breast cancer typically consist of?
4-6 cycles
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)
If a breast cancer patient has cardiac problems, what chemotherapies can we consider using?
Docetaxel
Cyclophosphamides (TC)
*avoid anthracyclines
What HER2 targeted therapy can be added on to a breast cancer patient’s chemo regimen for HER2+ disease?
Trastuzumab
Pertuzumab
How long should HER2 targeted therapy (Trastuzumab and Pertuzumab) be continued in breast cancer treatment?
1 year
What treatment should be added to the chemotherapy regimen for patients with Triple Negative Breast Cancer?
Immunotherapy
(pembrolizumab)
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
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
True or False: Combination chemotherapy in metastatic breast cancer patients has not been shown to be more effective
True
Which regimen in metastatic breast cancer is used only for HER2 low patients (1+)?
Fam-trastuzumab
Deruxtecan
What are the CDK 4/6 inhibitors?
Abemaciclib
Palbociclib
Ribociclib
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
At what age can you start having mammograms?
40
At what age should you start having annual mammograms?
45
What is the most common type of cancer in men?
Prostate cancer
Prostate cancer is driven by what?
Testosterone
(growth signal to the prostate)
Alterations in the androgen receptor
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
What are the methods used to diagnose prostate cancer?
Physical exam
PSA level
Biopsy of prostate
Transrectal ultrasound
Where are the most common places that prostate cancer will metastasize to?
Bone
Lung
Liver
What is the most common histology of prostate cancer?
Adenocarcinoma (99%)
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
What is the normal Prostate Specific Antigen (PSA) range?
0-4
What PSA level requires evaluation?
> 4
What PSA level is highly suspicious for malignancy?
> 10
What PSA velocity is suspicious for malignancy?
> 0.75 rise per year
What does m1 mean in prostate cancer?
metastatic
What does m0 mean in prostate cancer?
non-metastatic (only thing that is off is that the PSA is increasing)
What is HSPC?
Hormone sensitive prostate cancer
What is CRPC?
Castration resistant prostate cancer
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
What are the 2 types of radiation therapy that can be used in localized prostate cancer?
External beam
Brachy therapy (implanted pellets around prostate)
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)
For locally advanced/high risk prostate cancer, what treatment has been shown to be effective?
Androgen deprivation therapy with External beam radiation therapy
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
For localized prostate cancer, what is the definitive curative therapy?
Radical Prostatectomy (prostate removal) + Pelvic lymph node dissection (PLND)
What is the goal of androgen deprivation therapy?
Induce castration levels of testosterone
What drugs/drug class are considered Androgen Deprivation Therapy?
LHRH agonists
-Leuprolide
-Goserelin
True or False: LHRH agonists (leuprolide and goserelin) cause reversible castration in males with prostate cancer
True
What is the main toxicity associated with LHRH agonists?
Tumor flares (elevate hormones until receptors eventually shut down and cause castration)
What drug can be used instead of LHRH agonists in patients with cardiac history or need an oral drug?
Relugolix
What are the anti-androgen drugs?
Flutamide
Bicalutamide*****
Nilutamide
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
What are the 3 principles that should be considered in metastatic prostate cancer?
- Goal is palliation of disease and to suppress testosterone production
- Determine whether this is a PSA recurrence or overt metastatic disease
- Determine PSA doubling time
Which prostate cancer patients can consider using intermittent ADT therapy?
Men with biochemical failure only
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
What is the moa of enzalutamide?
Blocks androgen binding and translocation of androgen receptor
Who should enzalutamide be used with caution in?
Patients with seizure history
What is the moa of apalutamide?
Non-steroidal androgen receptor inhibitor
Which drug in prostate cancer is metabolized by CYP3A4?
Darolutamide
What is m1HSPC?
Prostate cancer that now has visceral metastases and is hormone sensitive
-determine therapy based on high or low volume
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
Which drug must be given with prednisone and why?
Abiraterone
-because it causes adrenal insufficiency (prednisone blocks this)
What is the moa of abiraterone?
Inhibits CYP17 which is an enzyme required for androgen synthesis
-inhibits testosterone precursor formation
What is the 1st line therapy for High Volume m1HSPC?
Docetaxel+ ADT
can also use:
ADT+Docetaxel+Abiraterone (+prednisone)
ADT+Docetaxel+Darolutamide
When do we consider using chemotherapy in prostate cancer treatment?
High Volume m1HSPC
What is the second-line chemotherapy that can be used in high volume metastatic prostate cancer?
Cabazitaxel
What drug can be used in prostate cancer tumors that express dMMR or MSI-H?
Pembrolizumab
How is goserelin administered?
Subq implant
How is leuprolide administered?
Subq or IM injection
At what age should men start screening for prostate cancer?
50
What PSA level indicated the need for annual screenings?
PSA>/= 2.5
WHat PSA level indicates the need for screening every 2 years?
PSA<2.5
EGFR mutations in lung cancer predict sensitivity to what?
Tyrosine kinase inhibitor (TKI) therapy
K-RAS mutations in lung cancer predict resistance to what?
Predict resistance to Tyrosine kinase inhibitors (TKI)
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)
Which form of lung cancer has a clear relationship to smoking?
Small cell lung cancer
Which form of lung cancer has rapid cell growth?
Small cell lung cancer
(this type of cancer responds well to chemo)
Which form of lung cancer has slow growth?
Non-small cell lung cancer
(moderate sensitivity to chemo and radiation)
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
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
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
Which form of lung cancer has a high risk of brain metastases?
Small Cell Lung Cancer
What is the treatment for small cell lung cancer extensive stage disease?
Platinum doublet chemo + Immunotherapy
Cisplatin + Etoposide +Atezolizumab/Durvalumab
What are the side effects of cisplatin?
Nausea/vomiting
Nephrotoxicity
Ototoxicity (do not use in patients with hearing loss)
Neuropathy
What drug can be used in patients with metastatic SCLC who have progressed on platinum-based therapy?
Pembrolizumab
What is the neoadjuvant regimen for resectable NSCLC?
Nivolumab + Platinum doublet (Cisplatin+Etoposide)
What is the adjuvant chemotherapy regimen for resectable NSCLC?
Non-squamous: Cisplatin + Pemetrexed
Squamous: Cisplatin + Gemcitabine, Cisplatin + Docetaxel
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)
What targeted therapy should be used in lung cancer patients with EGFR mutations (Exon 19 deletion, Exon 21 L858R mutation?
Osimertinib
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
What drug should be added on as subsequent therapy in patients with a K-RAS G12C mutation?
Sotorasib
In patients with PD-L1 positivity >/= 1% what treatment do we use?
Pembrolizumab
All mutation negative, non-squamous, NSCLC patients should receive what therapy?
Carboplatin + Pemetrexed + Pembrolizumab
What is the treatment for squamous NSCLC?
Pembrolizumab + Carboplatin + Paclitaxel
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
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
If a melanoma is a clinical stage IV, it should be tested for what?
BRAF V600E and K mutations
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
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
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
What is the most common side effect of Dabrafenib + Trametinib?
Pyrexia (fevers)
What did KEYNOTE-006 trial do?
Compared pembrolizumab with ipilimumab
-pembrolizumab has less toxicity
-pembrolizumab worked better
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
What age does screening for colorectal cancer start?
45
What 2 disease states increase the risk for development of colorectal cancer?
Ulcerative colitis
Crohn’s disease
(inflammatory conditions of the GI tract)
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)
What age does screening for colorectal start for patients with Familial Adenomatous Polyposis (FAP)?
10-12 years old
> 95% of colorectal cancers have what origin?
Adenocarcinomas (glands)
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)
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
What drugs are included in FOLFOX?
5-Flurouracil
Leucovorin
Oxaliplatin
What drugs are included in CapeOX?
Capecitabine
Oxaliplatin
What did the MOSAIC trial show?
FOLFOX significantly increased 6-year survival in colorectal cancer patients
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
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
If a patient with colorectal cancer has neuropathy, what drug may not be a good option for them?
Oxaloplatin
If a patient with colorectal cancer has a UGT1A1 deficiency, what drug needs to have its dose changed?
Irinotecan
KRAS mutations predict lack of response to which drugs?
anti-EGFR monoclonal antibodies
(do not use cetuximab or panitumumab)
Which two screening tests are used to detect colorectal cancer?
Fecal occult blood test (FOBT)
-high false negative rate
Fecal immunohistochemical test (FIT)
Which tests are used to detect colorectal cancer and advanced lesions?
Endoscopy (Colonoscopy)
Radiological exams
At what age should patients start being screened for colon cancer?
45
How often should a colonoscopy be done?
Every 10 years
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
What treatments are available to prevent colon cancer?
Cyclooxygenase inhibitors (celecoxib)
NSAIDs or Aspirin
Colectomy (if family history)
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
What genetic mutations increase the likelihood of getting ovarian cancer?
BRCA 1
BRCA 2
p53
What is Lynch II syndrome?
Hereditary nonpolyposis colorectal cancer
-Familial predisposition to colon cancer, endometrial cancer, and ovarian cancer
True or False: Most patients with Stage I and Stage II ovarian cancer are asymptomatic
True
*most patients present with advanced disease
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
How does ovarian cancer progress?
Starts in ovary and spreads throughout the peritoneal cavity (abdominal cavity)
True or False: Ovarian cancer responds well to chemo
True!
-but most patients will experience reoccurrence within the first 3 years
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
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
What is the standard chemotherapy regimen used in ovarian cancer?
Paclitaxel + Carboplatin every 3 weeks for 6 cycles
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
When taking carboplatin, what causes a Type IV reaction to develop?
-Delayed hypersensitivity reaction
-Occurs when antigen sensitized cells release cytokines after subsequent contact
How many cycles of carboplatin result in an increased risk of developing a Type IV hypersensitivity reaction?
> /= 8 cycles (this is considered repeat exposure)
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)
What is the biggest side effect associated with PARP inhibitors? (olaparib, niraparib, rucaparib)
Anemia
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
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
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
What is the first-line single agent used in patients who are platinum resistant?
Liposomal Doxorubicin
True or False: There are no effective screening tools for ovarian cancer
True
How do we diagnose skeletal related events?
Radionucleotide bone scan
