Oncology Anti-Tumor Agents Flashcards
Anthracyclines (7)
Daunorubicin Dactinomycin Doxorubcin Bleomycin Idarubicin Epirubicin Mitoxantrone
Anthracyclines Available agents (all IV): (5)
Doxorubicin Daunorubicin Idarubicin Epirubicin Mitoxantrone
Anthracyclines
Class side effects (5)
- Cardiotoxicity – acute and cumulative
- Myelosuppression
- Mucositis
- Extravasation
- Red urine (up to 48 hrs)
Anthracyclines (2)
Drug Interactions
Max lifetime dose
Hepatic metabolism
Avoid during radiation – these are radiation sensitizers
400 mg/m2
Liposomal Formulations (2)
Pros (2)
Cons (2)
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
Dactinomycin
Overview (2)
Cellphase
Dosage forms (1)
Cell phase non-specific
Vesicant: Watch for extravasation
Increased sensitization to radiation
o Avoid use with radiation
Dosage Forms: IV
Dactinomycin Side effects (3)
Myelosuppression
Photosensitivity
Hepatotoxicity
Vinca Alkaloids
MOA
Comes from…
One stops microtubule from coming apart and one stops the formation of it
Periwinkle plant
Vinca Alkaloids Available agents (3)
Vincristine
Vinblastine
Vinorelbine
Vinca Alkaloids
Dosage form
Administration
Can only be given IV
Can be given as IVP
Vinca Alkaloids (6) Side effects
- 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
Vinca Alkaloids
Special Considerations (2)
FATALITIES*
Vesicant! Vesicants are very irritating and can cause extravasations
Fatal if given intrathecally!
DO NOT MIX SYRINGES!!
Etoposide
Overview (2)
MOA (2)
- 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
Etoposide Dosage form (2) Side effects (4)
What kind of malignancies do you see with etoposide?
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
Etoposide (2)
Special Considerations
Irritant
Avoid rapid infusions
Taxanes
MOA (2)
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
Taxanes
Side effects/toxicity
- Myelosuppression
- Mucositis
- Neurotoxicty – peripheral neuropathy
- CYP 450 interactions (especially with carboplatin and cisplatin)
Taxanes
Paclitaxel (2)
- Infusion related reactions with paclitaxel use with premeds
- Drug interactions
Taxanes
Docetaxel (3)
- Fluid retention (pleural effusions, peripheral edema)
- Rash, nail changes
- Less infusion reactions because formulation lacks stabilizing agent
Camptothecins
Mechanism of Action
bind to topoisomerase I, which prevents completion of DNA spiraling and breaks DNA during replication
Camptothecins
Common agent used in pediatrics: and dosage forms (2)
Topotecan
- Dosage forms: IV, PO
Pegaspargase (Oncaspar®)
History (3)
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
Pegaspargase (Oncaspar®)
MOA
Dosage forms (2) Dose
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
Pegaspargase (Oncaspar®) Special Considerations (3)
Enzyme so do not shake! It will denature it
Max volume for IM injection is 2 ml
For IV administration run over 2 hrs
Pegaspargase (Oncaspar®) Side effects (5)
- 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
Pegaspargase (Oncaspar®)
If you have an allergic reaction to Pegaspargase
give Erwinaze®
Erwinaze® (asparaginase Erwinia chrysanthemi)
Overview (2)
Erwinia chrysanthemi is a gram (-) bacteria, member of the Enterobacteriaceae family but a plant pathogen.
Carries less risk of hypersensitivity reaction with the formulation
Erwinaze® (asparaginase Erwinia chrysanthemi)
Dosage form (2)
Dose (3)
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
Erwinaze® (asparaginase Erwinia chrysanthemi)
Contraindications (2)
Hypersensitivity to Erwinaze®
History of pancreatitis, hemorrhagic events or thrombosis with other L-asparaginase products (Oncaspar®)
Erwinaze® (asparaginase Erwinia chrysanthemi)
Side effects
similar to pegaspargase
Isotretinoin (Accutane®)
MOA
Used for…
Dosing
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
Isotretinoin (Accutane®) Side effects (5)
o Dry skin o Photosensitivity o Arthralgias o Increased LFTs o Differentiation syndrome
Isotretinoin (Accutane®)
NOTE
NOTE: it is a teratogen and women cannot take if they are pregnant or thinking about becoming pregnant
Interleukin-2 (IL-2, Aldesleukin®)
Overview (3)
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
Interleukin-2 (IL-2, Aldesleukin®)
Dosage forms
Dosage forms: IV
o Has very short half-life so it is giving as a cont infusion
Interleukin-2 (IL-2, Aldesleukin®) Side effects (4) Severe symptoms (2)
- 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
Interleukin-2 (IL-2, Aldesleukin®) Special considerations(2)
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)
Targeted therapy (5)
- Monoclonal antibodies (Rituxumab, Bevacizumab)
- IL-2
- mTOR inhibitors (Evirolimus)
- TK inhibitors (Imatinib, Sorafenib)
- 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
Rituxumab (Rituxan®)
Overview (3)
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
Rituxumab (Rituxan®)
Used for non-oncologic indications (3)
- Acute organ transplant rejection
- NMDA receptor encephalitis
- Rheumatoid arthritis
Rituxumab (Rituxan®)
Dosage form
Common dose
Dosage form: IV
- Common dose is 375 mg/m2
Rituxumab (Rituxan®)
BBW (3)
Infusion reactions – recommend premedication with antihistamine & Tylenol +/- steroids
Progressive multifocal leukoencephalopathy
Reactivation of Hepatitis B infections
Rituxumab (Rituxan®) Side effects (2)
o Fever
o Nausea, diarrhea
Bevacizumab (Avastin®)
MOA (2)
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
Bevacizumab (Avastin®)
Used for non-oncologic indications (1)
Retinopathy of prematurity
Bevacizumab (Avastin®)
Dosage form
Most common dose
Dosage form: IV, intravitreal
Common dose: 15 mg/kg (note it is weight not BSA based)
Bevacizumab (Avastin®)
BBW (4)
o GI perforation
o Impaired wound healing - avoid for at least 28 days following surgery
o Hemorrhage, thrombotic events
o PRES
Bevacizumab (Avastin®) Side effects (4)
o Nephritic syndrome – proteinuria, hypertension
o Hypertensive crisis
o Infusion reactions
o Dry skin
mTOR Inhibitors
MOA (3)
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
mTOR Inhibitors Other indications (1)
Prevention of acute organ transplant rejection
mTOR Inhibitors
Temsirolimus (Torisel®)
Dosage form
Drug Interactions
Dosage form: IV
Drug interactions
- CYP 3A4 Inhibitors (decrease dose 50%)
mTOR Inhibitors
Temsirolimus (Torisel®)
Side effects (7)
Rash Asthenia Mucositis N/V Edema, interstitial lung disease Hyperglycemia, hyperlipidemia Impaired wound healing, opportunistic infections
mTOR Inhibitors
Evirolimus (AFINITOR®)
Dosage form
PO
Tablets + dispersable formulation
mTOR Inhibitors
Evirolimus (AFINITOR®)
Dose depends on therapeutic monitoring: Therapeutic range
Therapeutic range: 5 – 15 ng/mL
mTOR Inhibitors
Evirolimus (AFINITOR®)
Drug interactions
CYP 3A4, 3A5, & 2C8 metabolism
mTOR Inhibitors
Evirolimus (AFINITOR®)
Side effects (4)
Non-infectious pneumonitis
Stomatitis, oral ulceration
Rash
Hyperglycemia, increased LFTs
Imatinib (GLEEVEC®)
Type
Dosage form + consideration (2)
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
Imatinib (GLEEVEC®) Side effects(3)
Fluid retention, edema, weight gain, pleural effusions
Hypotension
Increased LFTs
Warning signs of extravasation
4
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
Antineoplastic vesicants (4)
i. Cisplatin
ii. Anthracyclines
iii. Vinca alkaloids
iv. Dactinomycin
Treatment (3)
iPIV vs Central line
Antidote vs no antidote
For additional information – see UVa pharmacy guidelines
Pneumocystis jiroveci pneumonia (PCP) prophylaxis
Overview (2)
- 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
Pneumocystis jiroveci pneumonia (PCP) prophylaxis Available Options (2)
1 choice: Bactrim 5 mg/kg/day divided q12 3x per week
- Has a metallic taste
- Not tolerated well with younger children
Pneumocystis jiroveci pneumonia (PCP) prophylaxis Alternative options (2)
o Dapsone
o IV pentamidine
Nausea and Vomiting Associated with Chemotherapy
3 types
Anticipatory: A lot of it is anticipating the fact that you are going to vomit
Acute
Delayed
Nausea and Vomiting Associated with Chemotherapy
Overview
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
Granulocyte Colony Stimulating Factors (GCSF)
Overview (3)
- 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.
Risks with using GCSF in patients with cancer (2)
Theoretically can stimulate cancer cell proliferation
Avoid use in Acute leukemia patients!
Benefits of GCSF in the treatment of cancer
Neutropenia puts patients are risk for infection
ANC > 750 is typically required to administer myelosuppresive agents Stimulating WBC production min infection risk
Granulocyte Colony Stimulating Factors
Available agents
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
Granulocyte Colony Stimulating Factors
Side effects (1) Warnings (4)
Side effects
o Bone pain
Warnings o Splenic rupture o ARDS o Edema, capillary leak syndrome (Leukine®) o Anaphylactic reactions
Tumor Lysis Syndrome
Overview (3)
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
Tumor Lysis Syndrome
Most commonly associated with…
cytotoxic therapy
May occur spontaneously especially with high tumor burden
Tumor Lysis Syndrome
Tx and Prevention
o Hydration
o Allopurinol
o Rasburicase ($$$)
Allopurinol
MOA
BEST used prophylactically (2)
ADE (3)
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
Bleomycin
Cell Phase
MOA
Anti-tumor antibiotic
Cell phase nonspecific but works best in G phase
Break single strand DNA to reduce replication
Bleomycin Dosage forms (3)
IV, SC, intrapleural
Bleomycin Special Considerations (3)
not myelosuppressive
max lifetime dose = 400
pre-medication to minimize pyrogen release
Bleomycin Side effects (4)
Pulmonary toxicity (need baseline PFTs) – lung damage (Lance Armstrong
Mucositis
Skin hyperpigmentation
Hypersensitivity rxn with fever and chills to anaphylaxis
