Oncology Flashcards
1
Q
What is the most common type of cancer for both men and women?
A
Lung
2
Q
Define Incidence (Cancer)
A
number of new cases diagnosed with cancer in a specific period
3
Q
Define Mortality (Cancer)
A
number of cancer deaths in a specific period
4
Q
Define Prevalence (Cancer)
A
total number of people with cancer at a specific time
5
Q
What are 3 non-modifiable risk factors for cancer?
A
Age, Sex, Genetics
6
Q
What are some modifiable risk factors for cancer?
A
tobacco, sun exposure, alcohol consumption, physical inactivity, diet, obesity, vaccination (HPV/hepatitis), exposure to radiation, air pollution, radon gas
7
Q
What are 4 characteristics of cancer cells?
A
- exhibit uncontrolled growth
- ability to invade surrounding tissue
- exhibit decreased cellular differentiation
- ability to metastasize
8
Q
What are the most common sites for cancer to metastasize to?
A
liver, lung, bone and brain (LLBB)
9
Q
6 characteristics of benign tumours
A
- some degree of growth control
- encapsulated (non-invasive)
- localized
- typical of cell of origin (differentiated)
- indolent (slow growth)
- non-recurrent
10
Q
6 characteristics of malignant tumours
A
- uncontrolled growth
- invasive
- metastatic
- atypical (less differentiated)
- aggressive growth
- recurrent
11
Q
What does tumour grading determine?
A
aggressiveness
12
Q
What does tumour staging determine?
A
extent of disease
13
Q
What are the 3 categories that tumour staging encompasses?
A
- size of primary lesion (T)
- presence of lymph node involvement (N)
- presence of identifiable metastases (M)
14
Q
Why is cancer grading and staging important?
A
for prognosis, treatment planning, exchange of information, evaluation of treatment
15
Q
Biomarkers can be…. (4)
A
diagnostic, prognostic, predictive or used to monitor response
16
Q
What are the 4 pillars to cancer therapy
A
- surgery
- radiation
- cytotoxic & targeted therapies
- immunotherapy
17
Q
Which cancer therapy acts at a patient level?
A
immunotherapy
18
Q
When is surgery for cancer most effective?
A
for solid tumours (generally smaller)
19
Q
Why does radiation work in cancer?
A
rapidly dividing cells are very sensitive to ionizing radiation, so cancer cells are preferentially destroyed due to higher growth rate
20
Q
What is the general concept of targeted drug therapy?
A
block, inhibit or attack specific proteins that are involved in the molecular processes driving tumour cell growth
21
Q
What is the general concept of immunotherapy?
A
activate one’s immune system against a cancer
22
Q
What is the growth fraction?
A
number of cells in cycle / total number of cells in tissue
23
Q
As a tumour gets larger what happens to the growth fraction?
A
decreases
24
Q
What is the MOA of cytotoxic therapy (chemotherapy)?
A
interfere with the synthesis or function of DNA/RNA causing ‘apoptosis’ or programmed cell death
25
What is the role of the p53 suppressor gene?
senses DNA damage and activates other genes to repair the damage; if damage is irreparable, p53 will initiate cell death process (apoptosis)
26
What is the G1 phase of the cell cycle? How long is it?
growth and metabolism
6-12 hours
27
What is the S-phase of the cell cycle? How long is it?
DNA replication
6-8 hours
28
What is the G2 phase of the cell cycle? How long is it?
Growth of structural elements
3-4 hours
29
What is the M phase of the cell cycle? How long is it?
Mitosis
1 hour
30
What are the 5 classes of cytotoxic agents?
Alkylating agents
Anti-metabolites
Anti-tumour Antibiotics
Anti mitotic Agents
Topoisomearse Inhibitors
31
What are the two categories of cell cycle specific drugs?
Phase specific agents
Phase non-specific agents
32
How do phase non-specific agents work?
can inflict damage at any point in cell cycle
dose-dependent drugs
33
How do phase specific agents work?
schedule dependent drugs
34
How do cell cycle non-specific drugs work?
dose-dependent
35
What are goals of systemic therapy in cancer?
cure, improve survival, palliation
36
What is adjuvant chemotherapy?
Treatment given after primary treatment (surgery, radiation)
37
What is neo-adjuvant therapy?
Treatment given before primary treatment (surgery, radiation)
38
What is the purpose of adjuvant therapy?
To eliminate any microscopic cancer cells that may remain after the initial treatment, thereby reducing the risk of recurrence
39
What is the purpose of neo-adjuvant therapy?
To shrink the tumor, making it easier to remove or treat with other therapies
40
What is consolidation therapy?
Treatment of subclinical residual disease after induction therapy has produced a complete remission
41
What is salvage therapy?
treatment of relapse or refractory disease
42
What is conditioning therapy prior to stem cell transplant?
high doses of cytotoxic drugs are given that are lethal to bone marrow so we rescue with a stem cell transplant
43
What is lymphodepleting therapy prior to CAR T-cell Therapy?
Reduces the number of existing lymphocytes in the patient’s body, creating space for the infused CAR-T cells to effectively expand and fight cancer cells
44
What are some common chemotherapy toxicities?
bone marrow suppression, risk of infection, mucositis, stomatitis, hair loss or thinning, nausea or vomiting
45
What are advantages of combination chemotherapy?
higher cell kill, different MOAs, prevent or slow development of tumour resistance
46
What are disadvantages of combination chemotherapy?
multiple toxicities, may have to dose reduce in combination
47
What is the dose of many chemotherapy drugs based off of?
body surface area (BSA)
48
What is the dose of many monoclonal antibodies based off of?
mg/kg
49
What does the interval between doses of chemotherapy take into account?
recovery of host tissue toxicity, how fast the tumour is growing, MOA of drug
50
For adjuvant chemotherapy what is the duration of therapy?
prescribed number of cycles and duration
## Footnote
idk kinda dumb card but
51
For advanced disease what is the duration of chemotherapy?
usually given until evidence of disease progression or as long as toxicity can be managed
52
Why does chemotherapy sometimes fail?
- toxicity to normal cells
- patient comorbidities limit effective dosing
- first order kinetics of cell kill
- failure to detect tumour in early stage
- limited drug access to tumour site
- drug resistance (main reason)
53
What does first order kinetics of cell kill refer to?
there is a constant % of cells killed, not a constant number so theoretically cannot get 100% cell kill
54
What are the 4 types of drug resistance seen with cancer cells?
- tumor cell heterogeneity
- de novo
- selected
- acquired
55
Where do small molecule compounds act?
within a cancer cell
56
Where do monoclonal antibodies act?
outside of the cell
57
What is PD-1? What does it do?
checkpoint protein on immune cells (T cells). Normally acts as a type of "off switch" that helps keep the T cells from attacking other cells of the body
58
What is the MOA of PD-1 inhibitors? What does this do?
bind to PD-L1 on the tumour cell member or PD-1 on the T cell which blocks the binding of this receptor/ligand pair. Blocking this interaction between the tumour and T-cell helps the body's immune system recognize the cancer cells as unknown and target them for destruction by T-lymphocytes
59
What is endocrine therapy?
Treatment that uses hormones or substances that act like hormones to slow or stop the growth of cancer cells that depend on hormones to grow
60
Tamoxifen Drug Class/MOA
Selective Estrogen Receptor Modulator (SERM)
- binds to receptors in breast cancer cells preventing estrogen from binding and activating proliferation
61
Use of Tamoxifen
adjuvant and metastatic settings for hormone receptor (ER or PR) positive breast cancer
62
Tamoxifen is an estrogen ____ in breast tissue and an estrogen ____ in endometrium
antagonist, agonist
63
Tamoxifen Dose
20mg po once daily
64
How long do we generally use tamoxifen for in adjuvant setting? What is the exception?
5 years for low risk patients
may use it up to 10 years in pts that are high risk (cancer has spread to lymph nodes or is a very high grade tumour)
65
Tamoxifen side effects
flushing, hot flashes, hypertension, skin rash, fluid retention, nausea, mood changes (depression, fatigue), arthralgia, arthritis, vaginal discharge or dryness
66
Serious adverse effects of Tamoxifen
DVT, PE, Stroke
Uterine cancer
67
Tamoxifen drug interactions
- CYP2D6 inhibitors (bupropion, fluoxetine, etc.)
- anticoagulants
- grapefruit juice
68
Aromatase Inhibitors MOA
prevents conversion of androstenedione to estrone and conversion of testosterone to estradiol
69
Who do we use Aromatase Inhibitors in?
postmenopausal women in both adjuvant and metastatic breast cancer settings
70
If aromatase inhibitors are used in premenopausal women what also needs to be given/done?
ovarian suppression - GnRH agonists or oophorectomy
71
Anastrozole Drug Class
Aromatase Inhibitor
72
Letrozole Drug Class
Aromatase Inhibitor
73
Exemestane Drug Class
Aromatase Inhibitors
74
Which Aromatase inhibitor is steroidal and irreversible?
exemestane
75
ADR of Aromatase Inhibitors
osteopenia and osteoporosis, less risk of DVT than tamoxifen
hot flashes, flushing weakness, arthralgia, fatigue
76
What is goserelin acetate?
GnRH agonist
77
Why are GnRH agonists use in adjuvant breast cancer?
used for ovarian function suppression for premenopausal women at high risk for a new breast primary with hormone receptor positive disease to combine with aromatase inhibitor rather than tamoxifen alone
78
GnRH agonist use in metastatic breast cancer
used as a bridge to oophorectomy in premenopausal women
79
What is the most commonly diagnosed cancer in Canadian men?
prostate
80
What are the symptoms of prostate cancer?
difficulty urinating, dribbling after finishing urinating, urgency (esp at night), pain and blood during urination, difficulty having or maintaining an erection, unplanned weight loss, low appetite, pain or stiffness in the lower back, hips and/or pelvis
81
What are some risk factors for prostate cancer?
older age (>65), african american, family history, obesity
82
When using GnRH agonist in prostate cancer what happens when initiating? What do we do to manage?
initial flare of symptoms
must be co-prescribed with bicalutamide for initial 14-30 days
83
What is the maximum duration of therapy of GnRH agonists in prostate cancer?
3 years
84
Do GnRH antagonists reduce testosterone levels faster or slower than GnRH agonists?
generally faster
85
What are the main symptoms of a flare when initiating GnRH agonists for prostate cancer?
bone pain and urinary problems
86
What are some adverse effects of androgen deprivation therapy?
urinary symptoms, gynecomastia, decreased libido, hot flashes, erectile dysfunction, fatigue, weight gain, loss of muscle mass, osteopenia, osteoporosis
87
What is the MOA of abiraterone? What does this do?
selectively inhibits CYP17 - blocks androgen production in the testes, adrenal glands and tumour, decreases cortisol production which increases ACTH
88
What is required to be co-administered with abiraterone? Why?
prednisone (10mg/day) to prevent compensatory rise in ACTH
89
What does an increase in ACTH lead to?
accumulation of mineralocorticoids leading to hypertension, hypokalemia, edema
90
What are some examples of androgen receptor blockers?
bicalutamide, flutamide, enzalutamide, apalutamide
91
In addition to competitively inhibiting androgen from binding to the receptor what additional mechanism do enzlautamide and apalutamide have?
also inhibit nuclear translocation of the AR and inhibit AR-mediated binding to DNA
92
In naming MABs what does the substem designate
The target
93
In naming MABs what does xi mean
chimeric (part mouse)
94
In naming MABs what does zu mean?
humanized
95
What are chimeric monoclonal antibodies associated with more often compared to humanized?
infusion reactions
96
Humanized MAB contains how much human sequence
generally >90%
97
Chimeric MAB contains how much human sequence
generally >65%
98
What are 3 MAB targets of cell surface antigens?
CD20, EGFR, HER2
99
What is a plasma protein target for MABs?
Vascular Endothelial Growth Factor (VEGF)
100
What is the most common type of reaction to IV administered MABs?
Infusion reactions
101
What are signs and symptoms of infusion reactions?
fever and/or shaking chills, flushing and/or itching, alterations in HR and BP, dyspnea or chest discomfort, back or abdominal pain, N/V/D, skin rashes
102
What is cytokine release syndrome?
acute systemic inflammatory syndrome characterized by fever and multiple organ dysfunction
103
MOA of rituximab
anti-CD20
104
MOA of obinutuzumab
anti-CD20
105
What is important history to know about rituximab? (related to indication)
First anti-CD20 monoclonal antibody approved for the treatment of Non-Hodgkin's lymphoma
106
MOA and indication of Blinatumomab
anti-CD19/CD3; acute lymphoblastic leukemia (ALL)
107
MOA and indication of Dartumumab
anti-CD38 for multiple myeloma patients who are transplant ineligible and have received at least one prior to therapy
108
MOA of cetuximab
EGFR inhibitor
109
MOA of panitumumab
EGFR inhibitor
110
How do EGFR inhibitors work?
prevents the binding of EGF to the EGFR by physically blocking the ligand binding site on the receptor
111
What type of colorectal cancer is cetuximab indicated for?
non mutated - (wild type RAS) colorectal cancer
112
Bevacizumab MOA
VEGF inhibitor
113
What agents are used if colon cancer exists on the left side?
prefer to use cetuximab or panitumumab
114
What agents are used if colon cancer exists on the right?
bevacizumab
115
MOA of ramucirumab
VEGF inhibitor (high affinity for VEGFR2)
116
What are the two tests that can determine HER2 overexpression?
immunohistochemistry (IHC) or fluroscence in situ hybridization (FISH)
117
What two MABs can be used if breast cancer is HER2 positive?
Trastuzumab and Pertuzumab
118
Trastuzumab MOA
blocks HER2 dimerization
119
Pertuzumab MOA
blocks HER2 heterodimerization
120
What are ADC's?
antibody drug conjugates
121
What is T-DM1?
trastuzumab emtansine; an antibody drug conjugate
122
What makes an optimal ADC - antibody properties?
- target recognition unaltered compared with naked Ab
- abundant target expression and internalization
123
What makes an optimal ADC in terms of drug properties?
- highly potent cytotoxic agent
- validated mechanism of action
124
What makes an antibody drug conjugates in terms of linker properties?
- stable in plasma to avoid premature release of the drug
- labile once internalized to release the drug in its active form
125
What are growth factors?
growth factors are chemicals produced by the body that control cell growth
126
Where do Tyrosine Kinase Inhibitors work?
intracellularly
127
MOA of TKI's
TKIs block chemical messengers (enzymes) called tyrosine kinases which help to send growth signals in cells (blocking them stops the cell from growing and dividing)
128
Where do MABs work?
extracellularly
129
What is a cancer growth blocker?
targeted drug that blocks the growth factors that trigger cancer cells to divide and grow
130
What are the 4 types of cancer growth blockers?
TKIs, proteasome inhibitors, mTOR inhibitors, hedgehog pathway blockers
131
what class of medications are the
'-tinibs'
tyrosine kinase inhibitors
132
what class of medications are the
'-zomibs'
proteasome inhibitors
133
what class of medications are the
'-ciclibs'
cyclin-dependent kinase inhibitor
134
What class of medications are the
'-paribs'
PARP inhibitors
135
What class of medications are the
'-irolimus'
mTOR inhibitors
136
What is the pioneer TKI
imatinib
137
What are multi-TKI's
block more than one type of tyrosine kinase
138
What are the 4 TKI-EGFR inhibitors that can be used for NSCLC?
erlotinib, gefitinib, afatinib, osimertinib
139
Which TKIs are multi-targeted (general)?
VEGF
140
What is the EGFR T790M mutation?
the substitution of threonine by methionine at amino acid 790 on exon 20
141
What TKI is used for EGFR T790M mutation?
Osimertinib
142
What does ALK stand for? (as in ALK inhibitor)
anaplastic lymphoma kinase
143
ALK positive NSCLC is more common in who?
young patients who are non-smokers
144
What side effect are ALK inhibitors most commonly associated with?
GI toxicities (N/V/D)
145
What are the TKI ALK Inhibitors that are used in NSCLC? (5)
Alectinib, Brigatinib, Ceritinib, Crizotinib, Lorlatinib
146
What are the TKIs that target HER2? (3)
Lapatinib, Neratinib, Tucatinib
147
Sorafenib MOA
TKI - VEGF Inhibitor (among others as multi-TKI)
148
What is the master regulator of angiogenesis?
VEGF
149
ADR of the VEGF inhibitors sunitinib and pazopanib? (3 main)
hand foot skin reaction also called PPE
discolouration of the nails or hair
hypertension
150
What type of cancer is sorafenib used for? (most often)
metastatic hepatocellular carcinoma
151
What is the philadelphia chromosome?
translocation between chromosomes 9 and 22 forming the BCR-ABL fusion gene
152
What cancer is associated with having the Philadelphia chromosome?
Chronic Myelogenous Leukemia (CML)
153
What well known TKI is used for CML?
Imatinib
154
What are the drug interactions associated with TKI? (general)
CYP3A4
155
Imatinib ADR's
edema, hepatoxicity, bone marrow suppression
156
What is the purpose of the addition of MEK-inhibitor to BRAF inhibition in melanoma? (3)
synergistic effects, delays onset of drug resistance and improves tolerability
157
MOA and indication of Bortezomib
Proteasome inhibitor used in multiple myeloma
158
How do proteasome inhibitors work?
They inhibit proteasomes from working which causes a buildup of unwanted proteins in the cells, which makes the cancer cells die
159
What do proteasome inhibitors increase the risk of?
herpes zoster and herpes simplex virus reactivation
160
How do we reduce bortezomib-induced peripheral neuropathy?
using SC route over IV, scheduling (weekly instead of more frequently)
161
What can Vismodegib cause when administered to a pregnant women?
embryofetal death or severe birth defects
162
What happens if PARP enzymes are inhibited?
cancer cells lose one of their major mechanisms to repair single-stranded DNA breaks which decreases their viability
163
What can repair single stranded DNA breaks? What about double stranded?
PARP enzymes can repair single
BRCA gene proteins can repair double
164
What are PARP inhibitors generally used for?
gynaecological, breast and prostate cancers that specifically have BRCA gene mutation
165
Niraparib MOA
PARP inhibitor
166
Olaparib MOA
PARP inhibitor
167
What is the progression through different phases of the cell cycle controlled by?
a group of proteins called cyclins
168
What can dysregulation of CDK4 and CDK6 cause?
allows cancer cells despite genetic damage to progress through the G1 checkpoint to the S phase of the cell cycle
169
Abemaciclib MOA
CDK inhibitor
170
Palbociclib MOA
CDK inhibitor
171
Ribociclib MOA
CDK inhibitor
172
Which CDK inhibitor is continuous?
Abemaciclib
173
What is the major adverse effect with abemaciclib that occurs in 85% of patients?
diarrhea
174
Which CDK inhibitor is less likely to cause neutropenia?
Abemaciclib
175
Why are Palbociclib and Ribociclib not given continuously?
higher risk of neutropenia
176
Which CDK inhibitor has the highest risk of pneumonitis?
Abemaciclib
177
Which CDK inhibitor can cause QT prolongation?
Ribociclib
178
What side effect is equal for all CDK inhibitors (~25%)
Alopecia
179
What is the most common adult leukemia?
Chronic lymphocytic leukemia
180
MOA of Venetoclax
BCL-2 Inhibitor
181
What is the goal of immuno-oncology?
restore or enhance anti-tumour immune responses
182
Describe the cancer immunity cycle (7 steps)
1. Release of cancer antigens
2. Cancer antigen uptake and presentation
3. T cell priming and activation
4. T cell trafficking
5. Tumour infiltration
6. Recognition of cancer cells by T cells
7. Killing of cancer cells
183
What step of the cancer immunity cycle do Anti-CTLA-4s work at?
Step 3 - T cell priming and activation
184
What step of the cancer immunity cell cycle do anti PD-L1s and anti-PD-1s work at?
killing of cancer cells
185
What are the 6 types of immuno-oncology therapy?
- monoclonal antibodies
- adoptive T-cell transfer
- cytokines
- treatment vaccines
- Bacillus Calmette - Geurin (BCG)
- Toll like Receptor Agonists
186
Define/describe adoptive T-cell transfer
isolates and modifies T cells from tumour for enhanced immune response against cancer cells
ex) CAR-T cell therapy
187
What is Bacillus Calmette-Guerin (BCG)?
weakened form of tuberculosis bacteria and is used in bladder cancer to cause immune response against cancer cells
188
What are T-cells responsible for?
turning on and off the immune system
189
What type of receptors are CTLA-4 and PD-1?
inhibitory receptors
190
Ipilimumab MOA
CTLA-4 inhibitor
191
Pembrolizumab MOA
PD-1 inhibitor
192
Nivolumab MOA
PD-1 Inhibitor
193
Durvalumab MOA
PD-L1 inhibitor
194
Atezolizumab MOA
PD-L1 inhibitor
195
Avelumab MOA
PD-L1 inhibitor
196
Where and when do CTLA-4 inhibitors work in the T cell activation process?
act in the lymph nodes earlier in the process, during the priming phase
197
Where and when do PD-1 inhibitors work in the T cell activation process?
act directly in the cancer cell later in the process in the effector phase
198
What happens when CTLA-4 binds normally?
it inhibits T-cell activation, preventing excessive immune responses
199
What occurs when CTLA-4 inhibitors are used?
T cell proliferation and activation is enhanced - immune system activates
200
What are the 3 indications for CTLA-4 inhibitors?
melanoma, kidney cancer, small cell lung cancer
201
What happens when a T-cell binds PD-L1 on a tumour cell?
T cell doesn't recognize the tumour cell as foreign
202
What is flat dosing?
same dosing regardless of weight
203
What are adverse events that are common between chemotherapy and immunotherapy?
diarrhea, nausea, vomiting, fatigue
204
What are potential risk factors that favour the emergence of immune related adverse effects?
- personal/family history of autoimmune disease
- tumour infiltration
- concomitant medications and occupational exposures
205
What are some key factors for prevention of immune-related adverse effects?
- HCP and patient education
- patient reporting
- call-back program
206
In general terms what 3 things does the baseline assessment for immuno-oncology entail?
physical examination, lab tests, imaging
207
What is required during immuno-oncology treatment?
lab tests before every IO administration and compare values to baseline
208
What is required after IO treatment?
lab tests/evaluation on 3-month basis during first year and then every 6 months; be aware that AE's can develop even after discontinuation of treatment
209
What are the 3 potential etiologies of adverse effects a patient can experience?
- disease related
- incidental event
- immune-related adverse event
210
Grade 1 Immune Related AE:
Hospitalization?
Corticosteroids?
Other Immunosuppressive Drugs?
Immunotherapy?
No
Not recommended
Not recommended
Continue
211
Grade 2 Immune Related AE:
Hospitalization?
Corticosteroids?
Other Immunosuppressive Drugs?
Immunotherapy?
No
Topical or systemic (oral)
Not recommended
suspend temporarily; follow closely/proceed cautiously
212
Grade 3 Immune Related AE:
Hospitalization?
Corticosteroids?
Other Immunosuppressive Drugs?
Immunotherapy?
Yes
Systemic (oral or IV)
Consider for patients with unresolved symptoms after 3-5 days of steroid use; organ specialist referral advised
Suspend; discuss risk/benefit with patient before resumption
213
Grade 4 Immune Related AE:
Hospitalization?
Corticosteroids?
Other Immunosuppressive Drugs?
Immunotherapy?
Yes
Systemic (IV)
Consider for patients with unresolved symptoms after 3-5 days of steroid use; organ specialist referral
Discontinue permanently
214
When using steroids to manage immune related adverse events, how do we get a patient off of them?
taper steroids over >1 month after resolution of symptoms and improvement to grade 1 toxicity
215
What is a severe or steroid-refractory immune related adverse event?
no response to steroids within 48-72h may warrant additional immune suppressive agents
216
Does using systemic immunosuppressive agents impact the efficacy of immunotherapy?
No impact on efficacy or median or overall survival
217
Describe how CAR-T therapy works
Patients own cells are genetically engineered to specifically fight their cancer. T cells are extracted and engineered, body is preconditioned with chemo and the T-cells are reintroduced
218
What does CAR (as in CAR-Tcell therapy) stand for?
chimeric antigen receptor
219
3 Toxicities associated with CAR-T cell therapy?
B-cell aplasia
Cytokine Release Syndrome
Neurotoxicity
220
What is the 2nd leading cause of death in cancer patients?
cancer associated thrombosis
221
Who are LMWH preferred in for thrombosis prophylaxis?
patients at high risk of bleeding
patients with unresected intraluminal gastrointestinal (GI) or genitourinary (GU) cancer
patients with significant drug-drug interactions with DOACs
222
Who are DOACs preferred for in thrombosis prophylaxis?
patients at low risk of bleeding
patient with other cancer types (than GI or GU)
patients without significant drug-drug interactions
223
How long should cancer associated thrombosis prophylaxis treatment be?
generally 6 months as beyond is not associated with a decreased risk in DVT/PE (but is individualized)
224
Define cancer related fatigue
distressing, persistent, subjective sense of physical, emotional and/or cognitive tiredness or exhaustion related to cancer or cancer treatments that is not proportional to recent activity and interferes with usual functioning
225
What non-pharm can be done for cancer related fatigue?
- energy conservation
- exercise with moderate intensity
- limit naps
- reduce stress
- food and water intake
- use distractions
226
Define Chemotherapy urgent adverse events and provide examples
need to contact cancer clinic/health care team immediately
ex) temp changes, shivering, flu symptoms, nose or gum bleeding that doesn't stop, mouth sores that prevent eating or drinking, uncontrolled V/D, difficulty breathing, decreased urination/dark urine, anaphylaxis/infusion reaction
227
Chemotherapy Short Term Adverse Event Definition and provide examples
occurs during treatment, can often be managed with symptomatic care strategies or dose adjustments
ex) N/V/D, constipation, mucositis/stomatitis, myelosuppression, hair growth alterations, weight changes, taste/smell alterations, fatigue, hepatic/renal changes, cardiac function changes, hypertension, rash, skin and nail changes
228
Chemotherapy Long Term Adverse Events Definition and provide examples
May occur months to years after treatment stopped, recognition and treatment can be more difficult
Ex) infertility, secondary malignancies, heart failure, osteoporosis, pulmonary fibrosis, cataracts, peripheral neuropathy, hearing loss, fatigue, endocrine abnormalities
229
Adverse Event Grading Scale - Grades 0-5: what do they mean?
Grade 0 = none
Grade 1 = mild
Grade 2 = moderate
Grade 3 = severe
Grade 4 = life threatening
Grade 5 = death
230
What are the 3 of the most common toxicities experienced with chemotherapy?
stomatitis, diarrhea, nausea and vomiting
231
What are the preventative measures for hypersensitivity reactions?
use of pre-medications including the combination of a steroid, an H2 antagonist, an antihistamine and/or acetaminophen
232
What oncology drugs are most commonly associated with hypersensitivity reactions?
taxanes, platinums, bleomycin, and monoclonal antibodies
233
What are the 3 outcomes of myelosuppression?
neutropenia, thrombocytopenia, anemia
234
General symptoms of anemia
fatigue, malaise, SOB
235
Risks of Neutropenia
increased risks of bacterial, fungal and viral infections
236
General symptoms of thrombocytopenia
bruising and bleeding
237
What is the nadir in terms of hematologic toxicity? What does it depend on?
lowest point for blood cell counts
depends on the type of treatment
238
What is the management of chemotherapy induced anemia?
infusion of packed RBC's when Hgb <80g/L
239
Management of chemotherapy induced thrombocytopenia?
dose adjustment, treatment delays and/or platelet transfusion
240
What is the most common blood related adverse event from chemotherapy?
neutropenia
241
Define Neutropenia
ANC < 1.5 cells x 10^9/L
242
Management of Chemotherapy Induced Neutropenia
Dose reduction or treatment delay, prophylaxis with growth colony stimulating factors (GCSF's)
243
Define febrile neutropenia
Neutrophils <0.5 or <1.0 with a predicted decline to <0.5 within 48 hours
Fever with a single temp >38.3C or a temperature of >38C sustained for over 1 hour
244
What are risk factors for febrile neutropenia?
cytotoxic agent, dose intensity of the regimen, concomitant chemoradiation therapy, severity and duration of neutropenia, other patient factors
245
If a chemotherapy patient has a fever what should they not take? Why?
acetaminophen, ibuprofen, ASA until they've contacted a healthcare provider
often a fever is the only sign of infection in these patients, so do not want to use antipyretics before doing a full workup
246
What do we use for empiric treatment of febrile neutropenia?
broad spectrum antibiotics
anti-pseduomonal beta lactam: Pip-Taz, cefepime, meropenem or ceftazidime
247
When do we add on an agent to monotherapy antibiotic treatment of febrile neutropenia? What do we add?
add on vancomycin (or linezolid) if there is a high suspicion of gram positive involvement
- known MRSA carrier or past infection
- catheter related infection
- skin or soft tissue infection, severe mucositis
- hemodynamically unstable or septic
248
What is used for prevention and prophylaxis of febrile neutropenia?
filgrastim or pegfilgrastim (GCSF's)
249
MOA of Filgrastim and Pegfilgrastim
Growth Colony Stimulating Factor (GCSF) - regulates the release and promotes proliferation and differentiation of myeloid cells, including neutrophils
250
What is the main difference between filgrastim and pegfilgrastim?
pegylated is longer acting (allows for once weekly injection as opposed to daily)
251
When is primary prophylaxis recommended for febrile neutropenia?
when patient is at a greater than or equal to 20% risk for febrile neutropenia
252
When does mucositis most commonly present?
when the immune system is most vulnerable - during the neutrophil nadir (7-10s with cytotoxics)
253
What are risk factors for developing mucositis?
continuous chemotherapy infusions and concurrent radiation therapy
254
Treatment of chemotherapy induced mucositis
prescription mouth wash: steroids, local anesthetics, topical analgesics
fungal infection: nystatin, oral fluconazole
Analgesia
severe: hospitalization, IV narcotics, parenteral nutrition
255
Should we recommend Magic Mouthwash for chemotherapy induced mucositis? Why?
NO ABSOLUTLEY NOT
- lack of evidence
- expensive
- risk of nystatin resistance
- risk of steroid causing oral thrush
- risk of causing harm to patients
256
What are GI toxicities that can occur as a result of chemotherapy? (5)
Mucositis, Dyspepsia, Diarrhea, Constipation, Alterations of Taste/Smell
257
Management of chemotherapy induced dyspepsia
avoid aggravating factors
H2 blockers, PPIs, antacids
258
What can be used to manage chemotherapy induced diarrhea?
loperamide, diphenoxylate, octreotide
259
MOA of octreotide
somatostatin analogue - reduces fluid secretion from the stomach and intestine, increases fluid reabsorption from the intestine
260
MOA of loperamide and diphenoxylate
opioid analogues - reduces gut motility, reduces fluid secretion
261
What specific chemotherapy agent is known for causing diarrhea?
irinotecan
262
Acute Irinotecan Induced Diarrhea
When does it occur? What is its mechanism? Treatment?
occurs within 24 hours
Cholinergic mechanism
Atropine
263
Delayed Irinotecan Induced Diarrhea
When does it occur? What is its mechanism? Treatment?
occurring more than 24h after administration
secretory diarrhea - abnormal ion transport across injured intestinal mucosa that leads to increased water and electrolytes in GI tract
intensive loperamide regimen
264
What is the intensive loperamide regimen?
2 tablets at first onset of diarrhea, followed by 1 tablet scheduled every 2 hours during the day, 2 tablets every 4 hours during the night
can stop after diarrhea free for 12 hours
265
Pharm management for chemotherapy induced constipation?
stimulants, osmotic laxatives
266
What should generally be avoided to treat constipation in chemo patients?
enemas and suppositories as can introduce bacteria
267
What are some constipation warning signs?
no bowel movements for 3-5 days
not passing gas
blood in stool
foul smelling vomit
268
What is alterations of taste/smell described as in chemotherapy patients?
metallic or chemical taste
269
What skin changes can occur because of chemotherapy?
photosensitivity, nail changes, hyperpigmentation, dry skin, rashes, hand foot skin reaction
270
What is hand foot skin reaction also known as?
palmar plantar erythryodysethesia (PPE)
271
What drug is hand foot skin reaction most commonly encountered with?
capecitabine
272
Can we treat hand skin foot reaction?
No must prevent
273
How to prevent hand food skin reaction?
- avoid exposure to heat
- protective gloves and socks
- moisturizer BID
- avoid activities that apply pressure to skin of hands and feet
274
What hair changes can occur with chemotherapy?
depigmentation, change of color, change of texture, eyelash or eyebrow changes, alopecia
275
What are 3 agents that commonly cause hair loss (although there are many)
doxorubicin, paclitaxel, docetaxel
276
What does chemotherapy induced neurotoxicity most commonly manifest as?
peripheral neuropathy
277
Treatment of chemotherapy induced peripheral neuropathy
antidepressants, opioids, anticonvulsants
278
What are 3 agents that are associated with cardiotoxicty?
anthracyclines, fluoruracil, trastuzumab
279
What are some medical complications of not controlling chemotherapy induced N/V?
electrolyte imbalances, dehydration, anorexia, malnutrition, aspiration, pneumonia, esophageal tears, fractures
280
Chemotherapy Induced N/V - Goals of Therapy
No emesis
No (or mild) nausea
281
What are the 4 types of Chemotherapy Induced N/V?
Acute, Delayed, Anticipatory, Breakthrough
282
What is acute chemotherapy induced N/V? Main MOA
occurs within 24 hours of treatment
serotonin dependent
283
What is delayed chemotherapy induced N/V? Main MOA?
occurs 24-120 hours post treatment
substance P dependent
284
What is anticipatory chemotherapy induced N/V?
occurs as a conditioned response due to past negative experience (occurs prior to chemo)
285
What is breakthrough chemotherapy induced N/V?
occurs despite appropriate prophylactic anti-emetics and/or requires rescue agents
286
Why is it important to control acute phase of CINV (chemotherapy induced N/V)?
acute CINV is a predictor of delayed CINV and optimal up front control may translate to better long term control
287
Acute CINV - peripheral or central mechanisms
peripheral
288
Delayed CINV - peripheral or central mechanisms
central
289
What are some treatment related risk factors of acute CINV?
intrinsic property of drug - emetogenicity
dose, route, rate of infusion
repeated cycles
290
What are some patient related risk factors of acute CINV?
lower alcohol consumption, younger age, female
history of motion sickness
history of N/V during pregnancy
poor control with prior chemotherapy
291
What medication class is used for delayed phase of CINV?
NK1 antagonists
292
What medication class is used for acute phase CINV?
5-HT3 antagonists
293
What medication is used for anticipatory CINV?
Lorazepam
294
First Generation 5HT3 RA's (3)
ondansetron, dolasetron, granisetron
295
Second generation 5-HT3 RA (1)
palonestron
296
What improves the efficacy of serotonin receptor antagonists?
corticosteroids
297
Most common side effects with 5-HT3 RA antagonists
headache and constipation
298
When are 5-HT3 RAs most effective?
effective in first 24 hours post chemotherapy (acute phase) but not on days 2-5 post chemotherapy (delayed phase)
299
What are higher doses of first gen 5-HT3 RA's associated with?
QTc prolongation
300
What is the difference between second generation and first generation 5-HT3 RA's?
second generation has a longer half life and a 30-100 fold higher affinity for the 5HT3 receptor
301
MOA/Class of Ondansetron
5-HT3 Receptor Antagonist
302
What two medications are in Akynzeo
netupitant 300mg and palnestron 0.5mg
(NKI RA and 5HT3 RA)
303
What MOA/class do aprepitant and fosaprepitant fall into?
Neurokinin (NK-1) Receptor Antagonists
304
What do neurokinin receptor antagonists do?
blocks binding of substance P at the NK1 receptor in the CNS
305
What are DIs with NK-1 RA's?
Which medication specifically and what do we do to manage?
CYP3A4 and CYP2D6
Dexamethasone requires 50% dose reduction
306
Indications for Akynzeo (2)
The prevention of acute and delayed N/V associated with highly emetogenic chemotherapy
The prevention of acute nausea and vomiting associated with moderately emetogenic chemotherapy (MEC) that is uncontrolled by a 5-HT3 RA alone
307
For Highly Emetogenic Chemotherapy (HEC), including cisplatin based regimens what is the Day 1, 2, 3 and 4 dosing regimens
(Akynzeo and Dex)
Day 1: Akynzeo and Dex 12mg
Day 2-4: Dex 8mg
308
For Anthracycline-cyclophosphamide (AC) and chemotherapy not considered to be highly emetogenic (Also includes carboplatin (AUC >4)) what is the Day 1, 2, 3 and 4 dosing regimens (Akynzeo and Dex)
Day 1: Akynzeo and Dex 12mg
Day 2-4: Dex is not necessary
309
Common side effects of Akynzeo (although generally well tolerated)
headache, constipation, fatigue
310
Half life of palonestron
44 hours
311
What is the role of corticosteroids in CINV?
prevention of acute and delayed CINV - role is primarily in the delayed phase
312
What is the steroid of choice in CINV?
dexamethasone
313
High Risk Acute Emesis - Dex dose
20mg once
(12mg when used with fosaprepitant or netupitant)
314
High Risk Delayed Emesis - Dose of Dex
8mg BID for 3-4 days
(8mg once daily when used with fosaprepitant or netupitant)
315
Olanzapine Class
Atypical Antipsychotic or Thienobenzodiazepine (Second Generation)
316
Role of Olanzapine in CINV?
very effective in preventing delayed nausea
used for breakthrough N/V
317
Role of Dopamine Antagonists (metoclopramide, prochloperazine, haloperidol) in CINV
used in mild, moderate and highly emetogenic drugs - often used for breakthrough symptoms
318
Role of benzodiazepines in CINV?
lorazepam used for anticipatory emesis
319
Role of Cannabinoids and Medical Marijuana in CINV?
generally a limited role due to lack of clinical trials, modest antiemetic activity and unfavourable side effect profile
320
Define High Emetic Risk for IV Chemotherapy Agents
Risk in >90% of patients
321
Define Moderate Emetic Risk for IV Chemotherapy Agents
Risk in 30-90% of patients
322
Define Low Emetic Risk for IV Chemotherapy Agents
Risk in 10-30% of patients
323
Define Minimal Emetic Risk for IV Chemotherapy Agents
Risk in <10% of patients
324
2 Examples of IV Chemotherapy Agents that are High Emetic Risk
Anthracycline/cyclophosphamide combination
Cisplatin
325
Example of IV Chemotherapy Agent that is Moderate Emetic Risk
Carboplatin
326
Acute (Day 1) Therapy for High Non-AC and High AC Emetic Risk
4 drug regimen:
5-HT3, Dex, NK1 and Olanzapine
327
Acute (Day 1) Therapy for Moderate Emetic Risk Carboplatin >AUC 4 or Oxaliplatin women <50 years
5HT3, Dex, and NK1
328
Acute (Day 1) Therapy for Moderate Emetic Risk (that does not meet other criteria)
5HT3 and Dex
329
Delayed (Days 2-4) Therapy for High Non-AC Emetic Risk
Olanzapine and Dex
330
Delayed (Days 2-4) Therapy for High AC Emetic Risk
Olanzapine only
331
Delayed (Days 2-4) Therapy for Moderate, Low or Minimal Emetic Risk
No additional routine prophylaxis required
332
When is olanzapine suggested for breakthrough N/V?
if olanzapine was not previously used as prophylaxis
333
Common Strategies for Breakthrough Nausea and Vomiting
- move up to the next emetogenic level (if at moderate, move up to high)
- add one agent from a different class to the current regimen
- switch routes/dosage forms
- use of olanzapine is a good alternative
334
Treatment for anticipatory nausea (full regimen including instructions)
Lorazepam 0.5mg -1mg; has to be taken the night before treatment and repeated the next day 1-2 hours before anti-cancer therapy begins
335
Best approach for prevention of anticipatory N/V?
control of acute and delayed N/V
336
Risk Factors for Anticipatory N/V
- age younger than 50 years
- N/V after the last chemotherapy session
- post-treatment N/V described as moderate, severe, or intolerable
- feeling warm or hot all over after the last chemotherapy session
- susceptibility to motion sickness
- female
- high state anxiety
- history of morning sickness during pregnancy
- patient expectation of chemotherapy-related nausea before beginning treatment
- percentage of chemotherapy infusions followed by nausea
- high or moderate emetogenic potential of chemotherapy agents
