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Heme/Onc > Chemo toxicities > Flashcards

Chemo toxicities Flashcards

1
Q

What does the CTCAE categorize?

A

Adverse reactions to drugs

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2
Q

How often do cancer cells divide?

A

Every 0.5-2 days

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3
Q

What are the general types of chemotherapy toxicities?

A

Myelosuppression
GI toxicities
Infertility

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4
Q

What does myelosuppression cause?

A

Neutropenia
Anemia
Thrombocytopenia

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5
Q

What does GI toxicities cause?

A

N/V/D/mucositis

Taste changes

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6
Q

What are signs of neutropenia?

A

Infections

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7
Q

What are signs of anemia?

A

Fatigue

SOB

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8
Q

What are signs of thrombocytopenia?

A

Bleeding

Bruising

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9
Q

What are other signs of chemotherapy toxicities?

A

Alopecia
Rash, hyperpigmentation
Nail changes

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10
Q

What causes a decline in mature blood cells from chemotherapy?

A

Death of stem cells in the bone marrow

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11
Q

When is the risk of infection highest during chemotherapy?

A

Absolute Neutrophil Count less than/= to 500 cells

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12
Q

If there is a reduction in hgb, what symptom is increased during chemotherapy?

A

Fatigue

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13
Q

What level of platelets have an increased risk of bruising and bleeding?

A

< 50K

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14
Q

When is anticoagulation generally contraindicated for platelets?

A

< 30K

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15
Q

When do cell counts reach their lowest following chemotherapy?

A

7-14 days

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16
Q

What is the term for the lowest cell counts?

A

Nadir

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17
Q

What is supportive care for granulocytes during chemotherapy?

A

Prophylactic abx

Myeloid Growth Factors (MGF)

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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)

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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

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20
Q

What are MGFs?

A 
-stim = stimulators (all at least SQ)
Filgrastim
Filgrastim-sndz
Tbo-filgrastim
Pegfilgrastim
Sargramostim
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21
Q

What are the AEs of MGFs?

A

Mild-severe bone pain

NSAIDs (ibuprofen)

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22
Q

Who should receive MGF?

A

Pts w/at least a 20% chance of developing neutropenia

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23
Q

When is MGF administered?

A

Day after chemotherapy

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24
Q

Which MGFs com as an IV infusion?

A

Filgrastim

Sargramostin

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25
Q

How are MGFs supplied?

A 
Filgrastim: Vial/syringe
Filgrastim-sndz: syringe
Tbo-filgrastim: syringe
Pegfilgrastim: syringe/on-body injector
Sargramostim: vial
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26
Q

What deficiency must be repleted before ESA therapy?

A

Iron

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27
Q

What is the indications for ESAs?

A

Anemia d/t chemotherapy in cancer patients
Anemia of CKD
Symptomatic anemia secondary to melodysplastic syndrome

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28
Q

When do we initiate ESAs?

A

Hgb < 10
AND
Chemotherapy anticipated to continue at least 2 months
Continue until completion of chemo

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29
Q

What is the initial dose of erythropoetin?

A

150U/kg TIQ or 40,000U QW

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30
Q

What is the initial dose of darbepoetin?

A

2.25 mcg/kg QW

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31
Q

What is the MOA of ESAs?

A

Induces differentiation of committed erythroid progenitor cells

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32
Q

What are the risks of ESAs?

A

Cancer progression and shortened overall survival
Increased mortality secondary to venous and arterial thromboembolism
HTN

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33
Q

When are ESAs not recommended?

A

Patients with anemia secondary to chemotherapy being treated with curative intent

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34
Q

Which agents have the highest risk of infertility?

A

Non-cell cycle specific:
Alkylating
Anthracyclines

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35
Q

When will men’s sperm production resume?

A

In 1-4 years

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36
Q

Under what age has the greatest change of egg viability returning to normal?

A

Under 30 years

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37
Q

How long should women wait before attempting to conceive?

A

6 months

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38
Q

What are ways to manage infertility during chemotherapy?

A

Optimal birth control education
Sperm cryopreservation
Embryo/oocyte cryopreservation

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39
Q

Which chemotherapy agents are non-cell cycle specific?

A

Alkylating agents
Anthracyclines
Antitumor abx
Nitrosureas

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40
Q

What are limitations of non-cell cycle specific medications?

A

ALL cells are susceptible

Therapeutic w/MANY severe toxic effects

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41
Q

What are common toxic effects of non-cell cycle specific agents?

A 
Myelosupression
N/V/mucositis
Alopecia
Infertility
Nail/skin changes
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42
Q

During which phase do antimetabolites work?

A

S phase - mimic base pairs or inhibit formation of nucleotides, halting DNA replication

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43
Q

During which phase do taxanes and vincas work?

A

M phase - block the physical separation of cells

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44
Q

What are cell cycle specific agents?

A

Taxanes and vincas

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45
Q

What are limitations of cell cycle specific agents?

A 
Only affects actively replicating cells
Both therapeutic and patient specific/dose dependent toxic effects
Myelosuppression
N/V/D
Infertility (less)
Alopecia +/-
Nail/skin changes +/-
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46
Q

What frequency are cell cycle specific doses given?

A

More frequently (daily every 1-2 weeks) or as a continuous infusion

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47
Q

What frequency are non-cell cycle specific doses given?

A

Less frequently (every 3-4 weeks) and quickly

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48
Q

What can we give for mucositis?

A

Mouthwashes and rinses

Keratinocyte growth factor

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49
Q

What is the cumulative lifetime dose of doxorubicin?

A

450mg/m2

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50
Q

What do anthracyclines produce?

A

Superoxides (free radicals) that damage healthy cardiac tissue

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51
Q

Is LVEF dysfunction d/t anthracyclines reversible?

A

No

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52
Q

What is agent available for cardioprotection in patients taking anthracyclines?

A

Dexrazoxane

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53
Q

What are the indications for dexrazoxane?

A

Prevention of doxorubicin-induced cardiomyopathy in metastatic breast cancer patients exceeding life-time dose
Extravasation of any anthracycline agent

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54
Q

What is the MOA of dexrazoxane?

A

Binds to and sequesters superoxide molecules formed by anthracyclines

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55
Q

What are toxicities from dexrazoxane?

A

Myelosuppression
N/V
Hepatotoxicity
Injection site pain

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56
Q

What can dexrazoxane increase the risk of?

A

Cancer metastasis

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57
Q

Where does Bleomycin accumulate?

A

Lungs

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58
Q

What does bleomycin manifest as and is it reversible?

A

Pulmonary fibrosis; no

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59
Q

What is the lifetime cumulative dose of Bleomycin?

A

400 units

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60
Q

What should be monitored monthly with bleomycin?

A

PFTs

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61
Q

What is the MOA of ifosfamide/ cyclophosphamide?

A

Produce metabolite acrolein, which binds to and damages bladder cells

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62
Q

How does Nitrogen mustards’ hemorrhagic cystitis manifest?

A

Frank/microscopic blood in the urine

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63
Q

What is prophylaxis for nitrogen mustards’ hemorrhagic cystitis?

A

Hydration pre-/post- chemotherapy

Mesna

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64
Q

What is monitored with each dose of ifosfamide?

A

Urine RBCs

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65
Q

What are the indications of Mesna?

A

Prophylaxis of ifosfamide (on-label) or cyclophosphamide (off label) induced hemorrhagic cystitis

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66
Q

What is the MOA of Mesna?

A

Bind to acrolein, minimizing damage caused by the metabolite to the bladder

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67
Q

What are toxicities of Mesna?

A 
Flushing
Dizziness
Drowsiness
Injection site reaction
N/V/D/unpleasant taste(PO)
Arthralgias
Back pain
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68
Q

What lab may falsely be elevated with Mesna?

A

Ketones

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69
Q

What drugs cause peripheral neuropathy?

A

Platinums
Taxanes
Vincas

70
Q

How do platinums cause peripheral neuropathy?

A

Apoptosis of the dorasl root ganglion

71
Q

How do vincas cause peripheral neuropathy?

A

Loss of axonal microtubules

72
Q

How do taxanes cause peripheral neuropathy?

A

Perturbation of axonal transport secondary to excessive tubulin polymerization

73
Q

Is peripheral neuropathy reversible?

A

Yes, more difficult if not caught early

74
Q

What vitamin can be used as a preventative for peripheral neuropathy?

A

B6

75
Q

What drug classes can manage peripheral neuropathy?

A

SNRIs

GABA analogs

76
Q

What two toxicities does cisplatin cause?

A

Nephrotoxicity

Ototoxicity

77
Q

What is the mechanism that cisplatin causes nephrotoxicity?

A

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
Q

Giving aggressive what pre-and post- cisplatin therapy may prevent nephrotoxicity?

A

Fluids

79
Q

What is the mechanism of ototoxicity d/t cisplatin?

A

Damage from reactive O2 species to the cochlea

80
Q

Is nephro-/oto- toxicity d/t cisplatin reversible?

A

20-30% reduction in GFR may be permanent

Oto- usually permanent

81
Q

What are the indications of amifostine?

A

Prophylaxis of:

  • Xerostomia d/t radiation therapy (head/neck cancer)
  • Cisplatin induced nephrotoxicity (advanced ovarian cancer)
82
Q

What is the MOA of amifostine?

A

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
Q

How is amifostine administered?

A

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
Q

What are the toxicities of amifostine?

A

Hypotension
N/V
Anaphylaxis
SJS/TEN

85
Q

What chemo agents may cause centra neurotoxicity?

A

Nitrosureas
Ifosfamide
Cytarabine
MTX

86
Q

What are some nitrosureas?

A

Carmustine

Lomustine

87
Q

How do chemo agents cause central neurotoxicity?

A

Agents penetrate the BBB and cause direct toxicity to brain cells

88
Q

How does central neurotoxicity manifest?

A 
Seizures
Encephalopathy
Focal weakness
Stroke
Coma
89
Q

What additional toxicities manifest with cytarabine?

A

Cerebellar syndrome:

Speech, motor, and gait instability

90
Q

What is the indications for methylene blue?

A

Prophylaxis and treatment of ifosfamide-induced neurotoxicity

91
Q

What is the MOA of methylene blue?

A

Inhibits the formation of chloroacetaldehyde, a metabolite of ifosfamide that can penetrate the BBB

92
Q

When do we initiate methylene blue?

A

After trial of chemo d/c and fluid administration

93
Q

What is the dosing of methylene blue?

A

50 mg every 4-8 hours

94
Q

What are the toxicities of methylene blue?

A

Skin and body fluid discoloration (blue/green), dizziness, feeling hot, limb pain, nausea

95
Q

What is the MOA of MTX?

A

Inhibits dihydrofolate reductase, depriving cells of folate available for DNA production

96
Q

How can MTX be administered?

A

IV
PO
IT

97
Q

What is considered a HD MTX dose?

A

> 500 mg/m2

98
Q

What toxicities are associated with HD MTX?

A

Nephrotoxicity
Hepatotoxicity
Myelosuppression

99
Q

What must be monitored 24 hours after HD MTX administration?

A

Serum levels

100
Q

What is the indication for leucovorin?

A

Rescue of cells following HD IV MTX?

101
Q

What is the MOA for leucovorin?

A

Repletes folate needed for proliferation of bone marrow stem cells

102
Q

What is the dosing for leucovorin?

A

15mg IV/PO every 6 hours starting 24 hours after completion of MTX infusion

103
Q

Does leucovorin break down MTX or aid in clearance?

A

No

104
Q

What are the toxicities of leucovorin?

A 
Erythema
Pruritis
Rash
Urticaria
Hypersensitivity
105
Q

What is the indication for glucarpidase?

A

Treatment of MTX toxicity in cases of renal impairment

106
Q

What is the MOA of glucarpidase?

A

Recombinant enzyme that rapidly breaks down MTX into DAMPA and glutamate

107
Q

What is the dosing for glucarpidase?

A

50 units/kg IV x 1 hour w/in 96 hours of start of MTX infusion

108
Q

How long do we continue glucarpidase?

A

Continue leucovorin dosing even after glucarpidase administration until MTX level below threshold x 3 days

109
Q

How should leucovorin and glucarpidase be separated?

A

2 hours apart as it may compete with MTX for binding affinity

110
Q

How do we measure levels of MTX?

A

Chromatographic method

DAMPA interferes with immunoassay

111
Q

What are the toxicities of glucarpidase?

A

Allergic rxn (antibody development)

112
Q

What is the MOA of fluorouracil?

A

Binds to thymidylate synthase, inhibiting formation of nucleotides for incorporation into DNA

113
Q

What is the 1/2 life of fluorouracil?

A

16 minutes

114
Q

How does the adminsitration of leucovorin aid fluorouacil administration?

A

Tightens binding of 5FU to thymidylate synthase, increasing half-life

115
Q

What are the two ways fluorouracil can be dosed?

A

IV bolus 200-400 mg/m2

CIVI 2400-5000 mg/m2 over 46-96 hours

116
Q

What are the AEs of IV bolus fluorouracil?

A

Myelosuppression

117
Q

What are the AEs of CIVI fluorouracil?

A

D
Hand-foot syndrome
Mucositis

118
Q

What can overose/over-exposure cause?

A

Fatal myelosuppression and severe mucositis

119
Q

What is the indication of uridine triacetate?

A

Management of fluoropyrimidine overdose/over-exposure, regardless of presence of sx

120
Q

What is the MOA of uridine triacetate?

A

Provides uridine which directly antagonizes incorporation of fluorourdine triphosphate into RNA cell

121
Q

What is the dosing of uridine triacetate?

A

10g PO q6h x 20 doses w/in 96 hours after the end of fluorouracil/capecitabine adminsitration

122
Q

How can uridine triacetate be taken?

A

Mixed with applesauce, pudding, or yogurt prior to administration and followed with at least 120 ml of water

123
Q

What are the toxicities of uridine triacetate?

A

N/V/D

124
Q

What are the more severe sx of infusion reactions?

A

Hypotension
Bronchospasm, dyspnea
Syncope
Respiratory/Cardiac failure

125
Q

Which classes of chemotherapy agents have the most common infusion rxns?

A

Platinums

Taxanes

126
Q

If a patient has an allergy to paclitaxel, what solvent are they allergic to?

A

Cremaphor

127
Q

If a patient has an allergy to docetaxel/carbazitaxel, what solvent are they allergic to?

A

Polysorbate 80

128
Q

What additional sx may taxanes have with infusion rxns?

A

Back pain

129
Q

What AE may docetaxel have with the 1st or 2nd infusions?

A

Hypersensitivity rxns

Fluid retention

130
Q

What do we premedicate paclitaxel and carbazitaxel with?

A

Diphenhydramine
Dexamethasone
Famotidine

131
Q

What do we premedicate docetaxel with

A

Dexamethasone before, during, and after treatment

132
Q

Which class of chemo agents can patients have a true allergy to the drug itself?

A

Platinum

133
Q

How many administrations it take for platinum infusion reactions to typically occur?

A

After 6th administration

134
Q

What are additional sx of platinum infusion reactions?

A 
Disorientation
Visual disturbances
Ringing/pounding in ears
Unusual taste
Hallucinations
135
Q

Do we normally premedicate with platinum agents?

A

No, if we do we use dexamethasone starting with cycle 6

136
Q

What do mabs target?

A

Extracellular receptors and antigens

137
Q

How are mabs adminsitered?

A

IV

138
Q

How are mabs dosed?

A

Every 2-3 weeks

139
Q

What do nibs target?

A

Intracellular receptors

140
Q

How are nibs administered?

A

Orally

141
Q

How are nibs dosed?

A

Daily

142
Q

What is a major toxicity of tyrosine kinase inhibitors?

A

First pass metabolism - hepatotoxicity

143
Q

What is a common AE for HER-2 antagonism?

A

Cardiotoxicity

144
Q

Is HER-2 cardiotoxicity reversible?

A

Yes - hold ab or d/c

145
Q

What chemo agents should not be co-administered with HER-2 antagonists?

A

Anthracyclines

146
Q

What is monitoring for pertuzumab?

A

Baseline THEN
Every 6 weeks if neoadjuvant
Every 3 monthhs if metastatic

147
Q

What is monitoring for trastuzumab?

A

Baseline, then

Every 3 months

148
Q

What do we do with pertuzumab if LVEF < 45%, or 45-49% and >/= 10% below baseline?

A

Interupt therapy for >/= 3 weeks and repeat LVEF assessment

149
Q

When do we resume pertuzumab if it was held?

A

If > 49% or 45-49% with < 10% decrease below baseline

If no improvement at 3 weeks, d/c anti-HER2 therapy

150
Q

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?

A

Interrupt therapy for at least 4 weeks

Resume if LVEF returns to baseline w/in 4-8 weeks

151
Q

When do we d/c trastuzumab?

A

If persistent (greater than 8 weeks) LVEF decline or if therapy is held on more than 3 occasions for cardiomyopathy

152
Q

What types of cancer are EGFR antagonists used for?

A

Colorectal
Head and neck
Lung

153
Q

What does the binding of growth factor to EGFR cause?

A

Promotes cell growth and development

Prevent apoptosis

154
Q

What AEs does EGFR cause?

A

GI tract: D/N
Skin: acneiform rash
Lungs: cough, dyspnea, interstitial lung disease

155
Q

Is an acneiform rash cause by bacteria or an inflammatory reaction?

A

Inflammatory reaction

156
Q

What does the appearance of an Acneiform rash correlate with?

A

Efficacy of antineoplastic

157
Q

How is EGFR antagonism acneiform rash managed?

A

Sunscreen
Moisture
Steroid cream (systemic if severe)
Doxycycline/clindamycin

158
Q

During what stages of malignancy are VEGF antagonists approved per the FDA?

A

Metastatic

Unresectable

159
Q

What are AEs of VEGF antagonists?

A

Blood vessel lining: HTN, proteinuria, bleeding, impaired wound healing

160
Q

Which mab is a VEGF receptor antagonists?

A

Bevacizumab

161
Q

Which types of tumors are known to over-express targetable immune antigens?

A

B cell lymphomas and lymphocytic leukemias
Anaplastic large cell lymphoma
Hodgkins lymphoma
Chronic lymphocytic leukemia

162
Q

What chemo agents are CD19 specific?

A

Blinatumomab

163
Q

What chemo agents are CD20 specific?

A

Rituximab
Ofatumumab
Obinuzumab

164
Q

When do infusion reactions present with mabs?

A

1-2 adminsitrations

165
Q

What do we premedicate with for infusion reactions?

A

Tylenol and/or Benadryl depending on agent

166
Q

What are the checkpoints that immunotherapy works on?

A

CTLA-4
PD-1
PD-L1

167
Q

What are the CTLA-4 inhibitors?

A

Ipilimumab

168
Q

What are te PD-1 inhibitors?

A

Pembrolizumab

Nivolumab

169
Q

What are immune-mediated toxicities d/t?

A

Over stimulation of T cells

170
Q

How do we treat grade 2 or higher immune mediated toxicities?

A

Steroids (prednisone/ methylprednisolone)

171
Q

What type of cells do steroids target?

A

Activated T cells

Heme/Onc (20 decks)

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