Chemo toxicities Flashcards
(171 cards)
1
Q
What does the CTCAE categorize?
A
Adverse reactions to drugs
2
Q
How often do cancer cells divide?
A
Every 0.5-2 days
3
Q
What are the general types of chemotherapy toxicities?
A
Myelosuppression
GI toxicities
Infertility
4
Q
What does myelosuppression cause?
A
Neutropenia
Anemia
Thrombocytopenia
5
Q
What does GI toxicities cause?
A
N/V/D/mucositis
Taste changes
6
Q
What are signs of neutropenia?
A
Infections
7
Q
What are signs of anemia?
A
Fatigue
SOB
8
Q
What are signs of thrombocytopenia?
A
Bleeding
Bruising
9
Q
What are other signs of chemotherapy toxicities?
A
Alopecia
Rash, hyperpigmentation
Nail changes
10
Q
What causes a decline in mature blood cells from chemotherapy?
A
Death of stem cells in the bone marrow
11
Q
When is the risk of infection highest during chemotherapy?
A
Absolute Neutrophil Count less than/= to 500 cells
12
Q
If there is a reduction in hgb, what symptom is increased during chemotherapy?
A
Fatigue
13
Q
What level of platelets have an increased risk of bruising and bleeding?
A
< 50K
14
Q
When is anticoagulation generally contraindicated for platelets?
A
< 30K
15
Q
When do cell counts reach their lowest following chemotherapy?
A
7-14 days
16
Q
What is the term for the lowest cell counts?
A
Nadir
17
Q
What is supportive care for granulocytes during chemotherapy?
A
Prophylactic abx
Myeloid Growth Factors (MGF)
18
Q
What is supportive care for erythrocytes during chemotherapy?
A
Ruling out other causes of anemia
RBC transfusions when hgb < 7-8
Erythropoetin Stimulating Agents (ESAs)
19
Q
What is supportive care for platelets during chemotherapy?
A
Platelet transfusions when platelets < 20,000, or <50,000 in cases of planned surgery
20
Q
What are MGFs?
A
-stim = stimulators (all at least SQ) Filgrastim Filgrastim-sndz Tbo-filgrastim Pegfilgrastim Sargramostim
21
Q
What are the AEs of MGFs?
A
Mild-severe bone pain
NSAIDs (ibuprofen)
22
Q
Who should receive MGF?
A
Pts w/at least a 20% chance of developing neutropenia
23
Q
When is MGF administered?
A
Day after chemotherapy
24
Q
Which MGFs com as an IV infusion?
A
Filgrastim
Sargramostin
25
How are MGFs supplied?
```
Filgrastim: Vial/syringe
Filgrastim-sndz: syringe
Tbo-filgrastim: syringe
Pegfilgrastim: syringe/on-body injector
Sargramostim: vial
```
26
What deficiency must be repleted before ESA therapy?
Iron
27
What is the indications for ESAs?
Anemia d/t chemotherapy in cancer patients
Anemia of CKD
Symptomatic anemia secondary to melodysplastic syndrome
28
When do we initiate ESAs?
Hgb < 10
AND
Chemotherapy anticipated to continue at least 2 months
Continue until completion of chemo
29
What is the initial dose of erythropoetin?
150U/kg TIQ or 40,000U QW
30
What is the initial dose of darbepoetin?
2.25 mcg/kg QW
31
What is the MOA of ESAs?
Induces differentiation of committed erythroid progenitor cells
32
What are the risks of ESAs?
Cancer progression and shortened overall survival
Increased mortality secondary to venous and arterial thromboembolism
HTN
33
When are ESAs not recommended?
Patients with anemia secondary to chemotherapy being treated with curative intent
34
Which agents have the highest risk of infertility?
Non-cell cycle specific:
Alkylating
Anthracyclines
35
When will men's sperm production resume?
In 1-4 years
36
Under what age has the greatest change of egg viability returning to normal?
Under 30 years
37
How long should women wait before attempting to conceive?
6 months
38
What are ways to manage infertility during chemotherapy?
Optimal birth control education
Sperm cryopreservation
Embryo/oocyte cryopreservation
39
Which chemotherapy agents are non-cell cycle specific?
Alkylating agents
Anthracyclines
Antitumor abx
Nitrosureas
40
What are limitations of non-cell cycle specific medications?
ALL cells are susceptible
| Therapeutic w/MANY severe toxic effects
41
What are common toxic effects of non-cell cycle specific agents?
```
Myelosupression
N/V/mucositis
Alopecia
Infertility
Nail/skin changes
```
42
During which phase do antimetabolites work?
S phase - mimic base pairs or inhibit formation of nucleotides, halting DNA replication
43
During which phase do taxanes and vincas work?
M phase - block the physical separation of cells
44
What are cell cycle specific agents?
Taxanes and vincas
45
What are limitations of cell cycle specific agents?
```
Only affects actively replicating cells
Both therapeutic and patient specific/dose dependent toxic effects
Myelosuppression
N/V/D
Infertility (less)
Alopecia +/-
Nail/skin changes +/-
```
46
What frequency are cell cycle specific doses given?
More frequently (daily every 1-2 weeks) or as a continuous infusion
47
What frequency are non-cell cycle specific doses given?
Less frequently (every 3-4 weeks) and quickly
48
What can we give for mucositis?
Mouthwashes and rinses
| Keratinocyte growth factor
49
What is the cumulative lifetime dose of doxorubicin?
450mg/m2
50
What do anthracyclines produce?
Superoxides (free radicals) that damage healthy cardiac tissue
51
Is LVEF dysfunction d/t anthracyclines reversible?
No
52
What is agent available for cardioprotection in patients taking anthracyclines?
Dexrazoxane
53
What are the indications for dexrazoxane?
Prevention of doxorubicin-induced cardiomyopathy in metastatic breast cancer patients exceeding life-time dose
Extravasation of any anthracycline agent
54
What is the MOA of dexrazoxane?
Binds to and sequesters superoxide molecules formed by anthracyclines
55
What are toxicities from dexrazoxane?
Myelosuppression
N/V
Hepatotoxicity
Injection site pain
56
What can dexrazoxane increase the risk of?
Cancer metastasis
57
Where does Bleomycin accumulate?
Lungs
58
What does bleomycin manifest as and is it reversible?
Pulmonary fibrosis; no
59
What is the lifetime cumulative dose of Bleomycin?
400 units
60
What should be monitored monthly with bleomycin?
PFTs
61
What is the MOA of ifosfamide/ cyclophosphamide?
Produce metabolite acrolein, which binds to and damages bladder cells
62
How does Nitrogen mustards' hemorrhagic cystitis manifest?
Frank/microscopic blood in the urine
63
What is prophylaxis for nitrogen mustards' hemorrhagic cystitis?
Hydration pre-/post- chemotherapy
| Mesna
64
What is monitored with each dose of ifosfamide?
Urine RBCs
65
What are the indications of Mesna?
Prophylaxis of ifosfamide (on-label) or cyclophosphamide (off label) induced hemorrhagic cystitis
66
What is the MOA of Mesna?
Bind to acrolein, minimizing damage caused by the metabolite to the bladder
67
What are toxicities of Mesna?
```
Flushing
Dizziness
Drowsiness
Injection site reaction
N/V/D/unpleasant taste(PO)
Arthralgias
Back pain
```
68
What lab may falsely be elevated with Mesna?
Ketones
69
What drugs cause peripheral neuropathy?
Platinums
Taxanes
Vincas
70
How do platinums cause peripheral neuropathy?
Apoptosis of the dorasl root ganglion
71
How do vincas cause peripheral neuropathy?
Loss of axonal microtubules
72
How do taxanes cause peripheral neuropathy?
Perturbation of axonal transport secondary to excessive tubulin polymerization
73
Is peripheral neuropathy reversible?
Yes, more difficult if not caught early
74
What vitamin can be used as a preventative for peripheral neuropathy?
B6
75
What drug classes can manage peripheral neuropathy?
SNRIs
| GABA analogs
76
What two toxicities does cisplatin cause?
Nephrotoxicity
| Ototoxicity
77
What is the mechanism that cisplatin causes nephrotoxicity?
Direct toxicity from cisplatin and metabolites in proximal tubules
Epithelial dysfunction d/t reactive O2 species formed
Enhanced TNF-alpha and other cytokines in the kidney
78
Giving aggressive what pre-and post- cisplatin therapy may prevent nephrotoxicity?
Fluids
79
What is the mechanism of ototoxicity d/t cisplatin?
Damage from reactive O2 species to the cochlea
80
Is nephro-/oto- toxicity d/t cisplatin reversible?
20-30% reduction in GFR may be permanent
| Oto- usually permanent
81
What are the indications of amifostine?
Prophylaxis of:
- Xerostomia d/t radiation therapy (head/neck cancer)
- Cisplatin induced nephrotoxicity (advanced ovarian cancer)
82
What is the MOA of amifostine?
Metabolized into an active thiol which reduces cytotoxicity by binding to and detoxifying reactive O2 species of alkylating agents
Scavenger of free radicals formed by cisplatin and radiation
83
How is amifostine administered?
Hold all anti-HTNs 24h prior
Monitor BP every 5 minutes during therapy and periodically thereafter
Pre-medicated with dexamethasone and a 5HT-3 antagonist
84
What are the toxicities of amifostine?
Hypotension
N/V
Anaphylaxis
SJS/TEN
85
What chemo agents may cause centra neurotoxicity?
Nitrosureas
Ifosfamide
Cytarabine
MTX
86
What are some nitrosureas?
Carmustine
| Lomustine
87
How do chemo agents cause central neurotoxicity?
Agents penetrate the BBB and cause direct toxicity to brain cells
88
How does central neurotoxicity manifest?
```
Seizures
Encephalopathy
Focal weakness
Stroke
Coma
```
89
What additional toxicities manifest with cytarabine?
Cerebellar syndrome:
| Speech, motor, and gait instability
90
What is the indications for methylene blue?
Prophylaxis and treatment of ifosfamide-induced neurotoxicity
91
What is the MOA of methylene blue?
Inhibits the formation of chloroacetaldehyde, a metabolite of ifosfamide that can penetrate the BBB
92
When do we initiate methylene blue?
After trial of chemo d/c and fluid administration
93
What is the dosing of methylene blue?
50 mg every 4-8 hours
94
What are the toxicities of methylene blue?
Skin and body fluid discoloration (blue/green), dizziness, feeling hot, limb pain, nausea
95
What is the MOA of MTX?
Inhibits dihydrofolate reductase, depriving cells of folate available for DNA production
96
How can MTX be administered?
IV
PO
IT
97
What is considered a HD MTX dose?
> 500 mg/m2
98
What toxicities are associated with HD MTX?
Nephrotoxicity
Hepatotoxicity
Myelosuppression
99
What must be monitored 24 hours after HD MTX administration?
Serum levels
100
What is the indication for leucovorin?
Rescue of cells following HD IV MTX?
101
What is the MOA for leucovorin?
Repletes folate needed for proliferation of bone marrow stem cells
102
What is the dosing for leucovorin?
15mg IV/PO every 6 hours starting 24 hours after completion of MTX infusion
103
Does leucovorin break down MTX or aid in clearance?
No
104
What are the toxicities of leucovorin?
```
Erythema
Pruritis
Rash
Urticaria
Hypersensitivity
```
105
What is the indication for glucarpidase?
Treatment of MTX toxicity in cases of renal impairment
106
What is the MOA of glucarpidase?
Recombinant enzyme that rapidly breaks down MTX into DAMPA and glutamate
107
What is the dosing for glucarpidase?
50 units/kg IV x 1 hour w/in 96 hours of start of MTX infusion
108
How long do we continue glucarpidase?
Continue leucovorin dosing even after glucarpidase administration until MTX level below threshold x 3 days
109
How should leucovorin and glucarpidase be separated?
2 hours apart as it may compete with MTX for binding affinity
110
How do we measure levels of MTX?
Chromatographic method
| DAMPA interferes with immunoassay
111
What are the toxicities of glucarpidase?
Allergic rxn (antibody development)
112
What is the MOA of fluorouracil?
Binds to thymidylate synthase, inhibiting formation of nucleotides for incorporation into DNA
113
What is the 1/2 life of fluorouracil?
16 minutes
114
How does the adminsitration of leucovorin aid fluorouacil administration?
Tightens binding of 5FU to thymidylate synthase, increasing half-life
115
What are the two ways fluorouracil can be dosed?
IV bolus 200-400 mg/m2
| CIVI 2400-5000 mg/m2 over 46-96 hours
116
What are the AEs of IV bolus fluorouracil?
Myelosuppression
117
What are the AEs of CIVI fluorouracil?
D
Hand-foot syndrome
Mucositis
118
What can overose/over-exposure cause?
Fatal myelosuppression and severe mucositis
119
What is the indication of uridine triacetate?
Management of fluoropyrimidine overdose/over-exposure, regardless of presence of sx
120
What is the MOA of uridine triacetate?
Provides uridine which directly antagonizes incorporation of fluorourdine triphosphate into RNA cell
121
What is the dosing of uridine triacetate?
10g PO q6h x 20 doses w/in 96 hours after the end of fluorouracil/capecitabine adminsitration
122
How can uridine triacetate be taken?
Mixed with applesauce, pudding, or yogurt prior to administration and followed with at least 120 ml of water
123
What are the toxicities of uridine triacetate?
N/V/D
124
What are the more severe sx of infusion reactions?
Hypotension
Bronchospasm, dyspnea
Syncope
Respiratory/Cardiac failure
125
Which classes of chemotherapy agents have the most common infusion rxns?
Platinums
| Taxanes
126
If a patient has an allergy to paclitaxel, what solvent are they allergic to?
Cremaphor
127
If a patient has an allergy to docetaxel/carbazitaxel, what solvent are they allergic to?
Polysorbate 80
128
What additional sx may taxanes have with infusion rxns?
Back pain
129
What AE may docetaxel have with the 1st or 2nd infusions?
Hypersensitivity rxns
| Fluid retention
130
What do we premedicate paclitaxel and carbazitaxel with?
Diphenhydramine
Dexamethasone
Famotidine
131
What do we premedicate docetaxel with
Dexamethasone before, during, and after treatment
132
Which class of chemo agents can patients have a true allergy to the drug itself?
Platinum
133
How many administrations it take for platinum infusion reactions to typically occur?
After 6th administration
134
What are additional sx of platinum infusion reactions?
```
Disorientation
Visual disturbances
Ringing/pounding in ears
Unusual taste
Hallucinations
```
135
Do we normally premedicate with platinum agents?
No, if we do we use dexamethasone starting with cycle 6
136
What do mabs target?
Extracellular receptors and antigens
137
How are mabs adminsitered?
IV
138
How are mabs dosed?
Every 2-3 weeks
139
What do nibs target?
Intracellular receptors
140
How are nibs administered?
Orally
141
How are nibs dosed?
Daily
142
What is a major toxicity of tyrosine kinase inhibitors?
First pass metabolism - hepatotoxicity
143
What is a common AE for HER-2 antagonism?
Cardiotoxicity
144
Is HER-2 cardiotoxicity reversible?
Yes - hold ab or d/c
145
What chemo agents should not be co-administered with HER-2 antagonists?
Anthracyclines
146
What is monitoring for pertuzumab?
Baseline THEN
Every 6 weeks if neoadjuvant
Every 3 monthhs if metastatic
147
What is monitoring for trastuzumab?
Baseline, then
| Every 3 months
148
What do we do with pertuzumab if LVEF < 45%, or 45-49% and >/= 10% below baseline?
Interupt therapy for >/= 3 weeks and repeat LVEF assessment
149
When do we resume pertuzumab if it was held?
If > 49% or 45-49% with < 10% decrease below baseline
| If no improvement at 3 weeks, d/c anti-HER2 therapy
150
Wh do we do with trastuzumab if baseline LVEF > 55%, decrease in LVEF >/= 16% from pre-treatment value OR if baseline LVEF < 55%, decrease in LVEF >/= 10% from pre-treatment values?
Interrupt therapy for at least 4 weeks
| Resume if LVEF returns to baseline w/in 4-8 weeks
151
When do we d/c trastuzumab?
If persistent (greater than 8 weeks) LVEF decline or if therapy is held on more than 3 occasions for cardiomyopathy
152
What types of cancer are EGFR antagonists used for?
Colorectal
Head and neck
Lung
153
What does the binding of growth factor to EGFR cause?
Promotes cell growth and development
| Prevent apoptosis
154
What AEs does EGFR cause?
GI tract: D/N
Skin: acneiform rash
Lungs: cough, dyspnea, interstitial lung disease
155
Is an acneiform rash cause by bacteria or an inflammatory reaction?
Inflammatory reaction
156
What does the appearance of an Acneiform rash correlate with?
Efficacy of antineoplastic
157
How is EGFR antagonism acneiform rash managed?
Sunscreen
Moisture
Steroid cream (systemic if severe)
Doxycycline/clindamycin
158
During what stages of malignancy are VEGF antagonists approved per the FDA?
Metastatic
| Unresectable
159
What are AEs of VEGF antagonists?
Blood vessel lining: HTN, proteinuria, bleeding, impaired wound healing
160
Which mab is a VEGF receptor antagonists?
Bevacizumab
161
Which types of tumors are known to over-express targetable immune antigens?
B cell lymphomas and lymphocytic leukemias
Anaplastic large cell lymphoma
Hodgkins lymphoma
Chronic lymphocytic leukemia
162
What chemo agents are CD19 specific?
Blinatumomab
163
What chemo agents are CD20 specific?
Rituximab
Ofatumumab
Obinuzumab
164
When do infusion reactions present with mabs?
1-2 adminsitrations
165
What do we premedicate with for infusion reactions?
Tylenol and/or Benadryl depending on agent
166
What are the checkpoints that immunotherapy works on?
CTLA-4
PD-1
PD-L1
167
What are the CTLA-4 inhibitors?
Ipilimumab
168
What are te PD-1 inhibitors?
Pembrolizumab
| Nivolumab
169
What are immune-mediated toxicities d/t?
Over stimulation of T cells
170
How do we treat grade 2 or higher immune mediated toxicities?
Steroids (prednisone/ methylprednisolone)
171
What type of cells do steroids target?
Activated T cells
