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Pediatric Pharmacology Exam 2 > Oncology Anti-Tumor Agents > Flashcards

Oncology Anti-Tumor Agents Flashcards

1
Q

Anthracyclines (7)

A 
Daunorubicin
Dactinomycin
Doxorubcin 
Bleomycin
Idarubicin
Epirubicin
Mitoxantrone
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2
Q 
Anthracyclines
Available agents (all IV): (5)
A 
Doxorubicin
Daunorubicin
Idarubicin
Epirubicin
Mitoxantrone
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3
Q

Anthracyclines

Class side effects (5)

A
  • Cardiotoxicity – acute and cumulative
  • Myelosuppression
  • Mucositis
  • Extravasation
  • Red urine (up to 48 hrs)
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4
Q

Anthracyclines (2)
Drug Interactions

Max lifetime dose

A

Hepatic metabolism
Avoid during radiation – these are radiation sensitizers

400 mg/m2

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5
Q

Liposomal Formulations (2)
Pros (2)
Cons (2)

A

Doxorubicin & daunorubicin

Benefits
< cardiotoxicity: do see less toxicity, but there are greater infusion reactions
< extravasation risk

Cons
> infusion reactions
Plantar/palmar erythrodysesthesia (hand foot syndrome) – dose limiting

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6
Q

Dactinomycin
Overview (2)
Cellphase
Dosage forms (1)

A

Cell phase non-specific

Vesicant: Watch for extravasation

Increased sensitization to radiation
o Avoid use with radiation

Dosage Forms: IV

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7
Q 
Dactinomycin
Side effects (3)
A

Myelosuppression
Photosensitivity
Hepatotoxicity

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8
Q

Vinca Alkaloids
MOA

Comes from…

A

One stops microtubule from coming apart and one stops the formation of it

Periwinkle plant

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9
Q 
Vinca Alkaloids
Available agents (3)
A

Vincristine
Vinblastine
Vinorelbine

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10
Q

Vinca Alkaloids
Dosage form

Administration

A

Can only be given IV

Can be given as IVP

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11
Q 
Vinca Alkaloids (6)
Side effects
A
  • Neurotoxicities: Cumulative and reversible, but can be prolonged recovery
  • Constipation
  • Peripheral neuropathy: Give Gabapentin
  • Jaw pain
  • SIADH
  • Myelosuppression: Only with vinblastine and vinorelbine
    ♣ Benefit of vincristine is that it doesn’t cause this
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12
Q

Vinca Alkaloids
Special Considerations (2)
FATALITIES*

A

Vesicant! Vesicants are very irritating and can cause extravasations

Fatal if given intrathecally!

DO NOT MIX SYRINGES!!

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13
Q

Etoposide
Overview (2)
MOA (2)

A
  • Podophyllotoxin Derivatives
  • Compound originated from mandrake plants

Mechanism of Action
o G phase specific
o Binds to microtubules and actually accelerates growth, but does not allow for shrinking which leads to stabilization of the cell and it cannot divide

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14
Q 
Etoposide
Dosage form (2)
Side effects (4)

What kind of malignancies do you see with etoposide?

A

Dosage forms: IV, PO

Side effects

  • Mucositis
  • Hypotension: Acute drop in BP with infusions; Monitor vital signs and decrease rate if you notice a change
  • Hypersensitivity reactions
  • Myelosuppression
  • See secondary malignancies with use
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15
Q

Etoposide (2)

Special Considerations

A

Irritant

Avoid rapid infusions

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16
Q

Taxanes

MOA (2)

A

Compound originated from Pacific and European Yew trees

Mechanism of Action:
o Promotes microtubule assembly by binding to tublin; however does not allow dissolution of the tubules leading to cell arrest during apoptosis
o Cell phase specific

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17
Q

Taxanes

Side effects/toxicity

A
  • Myelosuppression
  • Mucositis
  • Neurotoxicty – peripheral neuropathy
  • CYP 450 interactions (especially with carboplatin and cisplatin)
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18
Q

Taxanes

Paclitaxel (2)

A
  • Infusion related reactions with paclitaxel use with premeds
  • Drug interactions
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19
Q

Taxanes

Docetaxel (3)

A
  • Fluid retention (pleural effusions, peripheral edema)
  • Rash, nail changes
  • Less infusion reactions because formulation lacks stabilizing agent
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20
Q

Camptothecins

Mechanism of Action

A

bind to topoisomerase I, which prevents completion of DNA spiraling and breaks DNA during replication

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21
Q

Camptothecins

Common agent used in pediatrics: and dosage forms (2)

A

Topotecan

- Dosage forms: IV, PO

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22
Q

Pegaspargase (Oncaspar®)

History (3)

A

First formulation originally found from E coli

ALL is one of the first cancers to be aggressively studied in pediatrics

Addition of asparagase during therapy significantly increased event free survival
- Elspar (L-asparaginase) is no longer available

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23
Q

Pegaspargase (Oncaspar®)
MOA

Dosage forms (2)
Dose
A

Mechanism of Action: Asparagase degrades asparagine (an essential amino acid in leukemic cells) depleting the cancer cells of building blocks for protein

Dosage forms: IV or IM
o Dose = 2500 Units/m2

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24
Q 
Pegaspargase (Oncaspar®)
Special Considerations (3)
A

Enzyme so do not shake! It will denature it

Max volume for IM injection is 2 ml

For IV administration run over 2 hrs

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25
Q 
Pegaspargase (Oncaspar®)
Side effects (5)
A
  • Anaphylaxis (bronchospasms, laryngeal edema, hypotension) epinephrine, methylpred should be at the bedside with administration
    Typically occurs after 1st cycle once patient has been sensitized
    Monitor for at least 60 min after each dose
    We do see all of these adverse effects, which causes delays in therapy or inability to use Oncaspar®
  • Thrombosis
  • Hepatotoxicty
  • Pancreatitis
  • Hyperglycemia
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26
Q

Pegaspargase (Oncaspar®)

If you have an allergic reaction to Pegaspargase

A

give Erwinaze®

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27
Q

Erwinaze® (asparaginase Erwinia chrysanthemi)

Overview (2)

A

Erwinia chrysanthemi is a gram (-) bacteria, member of the Enterobacteriaceae family but a plant pathogen.
Carries less risk of hypersensitivity reaction with the formulation

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28
Q

Erwinaze® (asparaginase Erwinia chrysanthemi)
Dosage form (2)
Dose (3)

A

Dosage Form: IM only

  • 2500 Units/m2 IM
  • 3x per weeks for 6 doses for each dose of pegaspargase
  • If volume is > 2mL it must be given in multiple sites
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29
Q

Erwinaze® (asparaginase Erwinia chrysanthemi)

Contraindications (2)

A

Hypersensitivity to Erwinaze®

History of pancreatitis, hemorrhagic events or thrombosis with other L-asparaginase products (Oncaspar®)

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30
Q

Erwinaze® (asparaginase Erwinia chrysanthemi)

Side effects

A

similar to pegaspargase

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31
Q

Isotretinoin (Accutane®)
MOA
Used for…
Dosing

A

All trans-retinoic acid, metabolized to active retinoic acid compound to promote cell differentiation

Used for neuroblastoma

Dosing = 80 mg/m2 daily x 14 days per cycle

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32
Q 
Isotretinoin (Accutane®)
Side effects (5)
A 
o	Dry skin
o	Photosensitivity
o	Arthralgias
o	Increased LFTs
o	Differentiation syndrome
33
Q

Isotretinoin (Accutane®)

NOTE

A

NOTE: it is a teratogen and women cannot take if they are pregnant or thinking about becoming pregnant

34
Q

Interleukin-2 (IL-2, Aldesleukin®)

Overview (3)

A

Recombinant human interleukin-2 gene; promotes proliferation of certain lymphocytic lines and killer cell activity as well as increased cytoxicity of lymphocytes.

The exact mechanism in cancer is less clearly defined

Currently used at UVa as part of neuroblastoma therapy with an investigational antibody

35
Q

Interleukin-2 (IL-2, Aldesleukin®)

Dosage forms

A

Dosage forms: IV

o Has very short half-life so it is giving as a cont infusion

36
Q 
Interleukin-2 (IL-2, Aldesleukin®)
Side effects (4)
Severe symptoms (2)
A
  • Fever, chills, flu like symptoms
  • Thrombocytopenia, leukocytosis
  • Elevated SCr and LFTs
  • Electrolyte abnormalities (Ca, Mg, phos)

Severe symptoms: capillary leak syndrome, anaphylaxis
o Not well tolerated

37
Q 
Interleukin-2 (IL-2, Aldesleukin®) 
Special considerations(2)
A

Recombinant product, so do not shake!

Requires close monitoring for side effects (Neuroblastoma therapy uses lower doses and typically experience significant side effects with higher doses)

38
Q

Targeted therapy (5)

A
  1. Monoclonal antibodies (Rituxumab, Bevacizumab)
  2. IL-2
  3. mTOR inhibitors (Evirolimus)
  4. TK inhibitors (Imatinib, Sorafenib)
  5. All of the above were broad category target sites; these are looking at what specifically we can make to target just one type of cell die
39
Q

Rituxumab (Rituxan®)

Overview (3)

A

Anti-CD20 chimeric monoclonal antibody

Binds to CD20 receptors on B cells to prevent cell cycle differentiation and cytotoxicity

Prolonged effects with B-cell depletion lasting 12 months

40
Q

Rituxumab (Rituxan®)

Used for non-oncologic indications (3)

A
  • Acute organ transplant rejection
  • NMDA receptor encephalitis
  • Rheumatoid arthritis
41
Q

Rituxumab (Rituxan®)
Dosage form
Common dose

A

Dosage form: IV

- Common dose is 375 mg/m2

42
Q

Rituxumab (Rituxan®)

BBW (3)

A

Infusion reactions – recommend premedication with antihistamine & Tylenol +/- steroids

Progressive multifocal leukoencephalopathy

Reactivation of Hepatitis B infections

43
Q 
Rituxumab (Rituxan®)
Side effects (2)
A

o Fever

o Nausea, diarrhea

44
Q

Bevacizumab (Avastin®)

MOA (2)

A

Anti-VEGF humanized monoclonal antibody

Binds to circulating VEGF proteins in blood preventing the binding of VEGF to andothelial cells. This leads to reduced production of blood vessels to the tumor site to prevent tumor progression

45
Q

Bevacizumab (Avastin®)

Used for non-oncologic indications (1)

A

Retinopathy of prematurity

46
Q

Bevacizumab (Avastin®)
Dosage form
Most common dose

A

Dosage form: IV, intravitreal

Common dose: 15 mg/kg (note it is weight not BSA based)

47
Q

Bevacizumab (Avastin®)

BBW (4)

A

o GI perforation
o Impaired wound healing - avoid for at least 28 days following surgery
o Hemorrhage, thrombotic events
o PRES

48
Q 
Bevacizumab (Avastin®)
Side effects (4)
A

o Nephritic syndrome – proteinuria, hypertension
o Hypertensive crisis
o Infusion reactions
o Dry skin

49
Q

mTOR Inhibitors

MOA (3)

A

mTOR = mammalian target for rapamycin

Mechanism of Action
o Inhibition of PI3K–Akt–mTOR pathway
- Binds to a protein that will further inhibit a cell signaling pathway of cell regulation and growth leading to cytotoxicity

o Results in modulation of cellular metabolism, growth, proliferation, and angiogenesis & ultimately cytotoxicity

o May also sensitize cancer cells to chemotherapy

50
Q 
mTOR Inhibitors
Other indications (1)
A

Prevention of acute organ transplant rejection

51
Q

mTOR Inhibitors
Temsirolimus (Torisel®)
Dosage form
Drug Interactions

A

Dosage form: IV

Drug interactions
- CYP 3A4 Inhibitors (decrease dose 50%)

52
Q

mTOR Inhibitors
Temsirolimus (Torisel®)
Side effects (7)

A 
Rash
Asthenia
Mucositis
N/V
Edema, interstitial lung disease
Hyperglycemia, hyperlipidemia
Impaired wound healing, opportunistic infections
53
Q

mTOR Inhibitors
Evirolimus (AFINITOR®)
Dosage form

A

PO

Tablets + dispersable formulation

54
Q

mTOR Inhibitors
Evirolimus (AFINITOR®)
Dose depends on therapeutic monitoring: Therapeutic range

A

Therapeutic range: 5 – 15 ng/mL

55
Q

mTOR Inhibitors
Evirolimus (AFINITOR®)

Drug interactions

A

CYP 3A4, 3A5, & 2C8 metabolism

56
Q

mTOR Inhibitors
Evirolimus (AFINITOR®)

Side effects (4)

A

Non-infectious pneumonitis
Stomatitis, oral ulceration
Rash
Hyperglycemia, increased LFTs

57
Q

Imatinib (GLEEVEC®)
Type
Dosage form + consideration (2)

A

Type of tyrosine kinase inhibitor

Dosage form: PO
o Do not crush, but can be dissolved in water or apple juice
o Requires renal and hepatic dose adjustments

58
Q 
Imatinib (GLEEVEC®)
Side effects(3)
A

Fluid retention, edema, weight gain, pleural effusions
Hypotension
Increased LFTs

59
Q

Warning signs of extravasation

4

A

i. Pain (does not always occur)
ii. Patient complains of burning, tingling, funny feeling at infusion site
iii. Signs of infiltration near infusion site
iv. Redness, erythema at infusion site

60
Q

Antineoplastic vesicants (4)

A

i. Cisplatin
ii. Anthracyclines
iii. Vinca alkaloids
iv. Dactinomycin

61
Q

Treatment (3)

A

iPIV vs Central line
Antidote vs no antidote
For additional information – see UVa pharmacy guidelines

62
Q

Pneumocystis jiroveci pneumonia (PCP) prophylaxis

Overview (2)

A
  • Pneumocystis jiroveci is an opportunistic fungus that infects immunocompromised hosts
  • All patients who receive chemotherapy are at increased risk of opportunistic infections and therefore should be on PCP prophylaxis
63
Q 
Pneumocystis jiroveci pneumonia (PCP) prophylaxis
Available Options (2)
A

1 choice: Bactrim 5 mg/kg/day divided q12 3x per week

  • Has a metallic taste
  • Not tolerated well with younger children
64
Q 
Pneumocystis jiroveci pneumonia (PCP) prophylaxis
Alternative options (2)
A

o Dapsone

o IV pentamidine

65
Q

Nausea and Vomiting Associated with Chemotherapy

3 types

A

Anticipatory: A lot of it is anticipating the fact that you are going to vomit

Acute

Delayed

66
Q

Nausea and Vomiting Associated with Chemotherapy

Overview

A

Mild to severe (r/q admission for IV hydration)

Nausea and vomiting is a common and concerning side effects of chemotherapy. Some agents are more emetogenic than others

67
Q

Granulocyte Colony Stimulating Factors (GCSF)

Overview (3)

A
  • Since so many chemotherapy agents cause bone marrow suppression, GCSF can help so that bone marrow production and proliferation is induced
  • Theoretical risk that it can stimulate cancer (ALL)
  • G-CSF is a natural hormone found in monocytes, fibroblasts, and endothelial cells. Binds to hematopeotic cells to induce cells production and proliferation.
68
Q

Risks with using GCSF in patients with cancer (2)

A

Theoretically can stimulate cancer cell proliferation

Avoid use in Acute leukemia patients!

69
Q

Benefits of GCSF in the treatment of cancer

A

Neutropenia puts patients are risk for infection

ANC > 750 is typically required to administer myelosuppresive agents Stimulating WBC production min infection risk

70
Q

Granulocyte Colony Stimulating Factors

Available agents

A

Available agents
Filgrastim (Neupogen®, IV, SC)
- Given daily

Pegfilgrastim (Neulasta®)
- Prolonged half-life (15 – 80 hrs)

Sargomigrastim (Leukine®, GMCSF)
- IV over 24 hrs or SC daily

71
Q

Granulocyte Colony Stimulating Factors

Side effects (1)
Warnings (4)
A

Side effects
o Bone pain

Warnings
o Splenic rupture
o ARDS
o Edema, capillary leak syndrome (Leukine®)
o Anaphylactic reactions
72
Q

Tumor Lysis Syndrome

Overview (3)

A

Rapid cell death resulting in nucleic acid release and metabolism to uric acid

Increased uric acid (N/V, lethargy, uretal obstruction 2/2 uric acid crystal deposition in renal tubules)

Hyperphosphatemia, hyperkalemia

73
Q

Tumor Lysis Syndrome

Most commonly associated with…

A

cytotoxic therapy

May occur spontaneously especially with high tumor burden

74
Q

Tumor Lysis Syndrome

Tx and Prevention

A

o Hydration
o Allopurinol
o Rasburicase ($$$)

75
Q

Allopurinol
MOA

BEST used prophylactically (2)

ADE (3)

A

MOA
- Decreases production of uric acid by inhibiting xanthine oxidase

BEST when used prophylactically

  • High tumor burden
  • Cytotoxic therapy

Adverse Effects

  • Rash
  • Increased LFTs
  • Increased alkaline phosphatase
76
Q

Bleomycin
Cell Phase

MOA

A

Anti-tumor antibiotic
Cell phase nonspecific but works best in G phase

Break single strand DNA to reduce replication

77
Q 
Bleomycin 
Dosage forms (3)
A

IV, SC, intrapleural

78
Q 
Bleomycin
Special Considerations (3)
A

not myelosuppressive
max lifetime dose = 400
pre-medication to minimize pyrogen release

79
Q 
Bleomycin
Side effects (4)
A

Pulmonary toxicity (need baseline PFTs) – lung damage (Lance Armstrong
Mucositis
Skin hyperpigmentation
Hypersensitivity rxn with fever and chills to anaphylaxis

Pediatric Pharmacology Exam 2 (9 decks)

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