Chemotherapy Flashcards
How is chemotherapy classified?
Either cell cycle phase-specific or non-specific
What is a drug that is cell-cycle specific?
Something that affects DNA replication or mitosis
What is a drug that is cell cycle non-specific?
Something that has generalized DNA damage no matte what cell cycle it is in
Why do we care if a chemo drug is cell cycle specific or non-specific?
We care about this because tumor will have various stages of the cell cycle. If you give a drug that is cell cycle non-specific you will potentially affect every cell in that tumor. Cell cycle specific will only cover those that it specifically will work against based on the stage it is in and you will potentially affect fewer cells in the tumor
Which cell cycle is relatively resistant to drugs?
G0
What is chemo effective against?
Rapidly dividing cells (neoplastic ells, BM cells, and enterocytes)
What are the indications for use of chemotherapy?
a Used for systemic disease:
Surgery and radiation are used for things that have not yet metastasized to other parts of the body
Whole body disease (lymphoma, multiple myeloma)
Metastasis
What are the rare exceptions for chemo use that is not systemic?
Intracavitary
Intralesional
Electrochemotherapy
What is chemo used as a primary therapy for?
Systemic tumors
What is chemo used as an adjuvant therapy (after definitive treatment) for?
Highly metastatic tumors
Dirty margins
What is chemo used as an neoadjuvant therapy (before definitive treatment) for?
Shrink tumor prior to surgery
How is chemo used for palliation?
Help the patient feel better
Maintain stable disease if the patient’s current quality of life is okay
How is chemo dosed?
Mg/m^2
In small patients, it will be mg/kg
What may cause adjustments to the chemo dose?
Body size Adverse events (febrile neutropenia, high grade GI upset, Decreases 10-15%)
What is dose escalation?
If we are not hitting the bone marrow hard enough, are we actually doing anything to the tumor? May dose escalate if this is the case
What are the broad issues associated with compounded drugs?
Legality
Quality control
Client education regarding risks vs benefits
Stability
What are the legality issues with compounded drugs?
Cannot compound a commercially-available product/strength or within +/- 10% strength
Cannon compound solely to affect price
What is the issue with quality control in compounded drugs?
Not evaluated for FDA for safety/efficacy
What are the routes of accidental chemo exposure?
Ingestion
Direct contact (syringe, counters, vials, animal waste)
Inhalation
What is a closed system drug transfer device and why is it used?
Used to prepare chemo safely
Gives a way to get the syringe to the vial without the chemo getting outside of the vial and into the environment
What are the safety issues associated with chemo?
It is teratogenic, mutagenic, and carcinogenic
Risks associated with preparation and administration
Adverse effects are observed at low exposure levels
Consequences include: rash, headache, hair loss, reproductive problems, cancer
What are the breeds affected by MDR-1/ABCB-1 gene?
Collie (70%)
Long-haired whippet (65%)
Australian Shepherd (standard and mini) (50%)
Silken Windhound, McNab (30%)
Shetland Sheepdog, English Shepherd (15%)
GSD (10%)
Old Eng. Sheepdog, Border Collie, mixed breeds (5%)
What does MDR-1/ABCB-1 gene encode for?
P-glycoprotein pump
What does the p-glycoprotein pump do?
This pump removes drugs from the body
What does bone marrow suppression affect?
Neutrophils, then platelets, then RBCs
This will usually occur 7-10 days post treatment
What is nadir?
The lowest cell count obtained after chemo
The worst typically 1 week after treatment begins
When are antibiotics indicated?
If neutrophils are <1000/μl because the patient is more susceptible to infection
What is the mechanism of action of alkylating agents?
Alkyl group covalently bind to DNA
DNA alkylation causes base pair mismatch and strand breakage of DNA
Cell cycle non-specific
What is the mechanism of action of platinum drugs?
Platinum group intercalates into DNA
Creates interstrand and intrastrand cross-links
Rigid fixation of the drug forces DNA strand to bend/kink
This interferes with the ability of DNA polymerase to come in and move things around
Cell cycle non-specific
What is the mechanism of action of anthracyclines?
Bind to topoisomerase II Prevent re-sealing of DNA nicks --> SS and DS breaks Intercalation into DNA Additional doxorubicin effects: Free radical generation Effects on cell membranes
What is the mechanism of action of vinca alkaloids?
Inhibit microtubule formation
Interference with mitotic spindle
Disruption of mitosis; division arrest
Cell cycle specific (M phase)
What is the mechanism of action of palladia?
Receptor tyrosine kinase inhibitors Inhibition of receptor --> decreases: Cell proliferation Cell cycle progression Cell migration Cell survival
What is the mechanism of action of L-asparaginase?
Depletion of asparagine stores –> inhibits protein synthesis
Selective for neoplastic lymphocytes
What is the unique side effect of 5-Fluorouracil (5FU)?
Fatal neurotoxicity in cats
What are unique side effects of rabacfosadine (Tanovea)?
Dermatopathies
Grade 5 pulmonary fibrosis
What are unique side effects of vincristine (Oncovin)?
Peripheral neuropathy
Ileus (cats > dogs)
What are unique side effects of vinblastine (Velban)?
Rare peripheral neuropathy
What are unique side effects of vinorelbine (Navelbine)?
Rare peripheral neuropathy
Derm lesions
What are unique side effects of cisplatin (Platinol)?
Fatal pulmonary toxicity in cats: “Cisplat splats cats”
Nephrotoxic: Has to be given with aggressive diuresis because of this
Ototoxic
What are unique side effects of carboplatin (Paraplatin)?
Sterile hemorrhagic cystitis (very rare)
What are unique side effects of mechlorethamine?
Severe vesicant
What are unique side effects of cyclophosphamide (Cytoxan)?
Sterile hemorrhagic cystitis (this drug is the poster child for this)
What are unique side effects of CCNU (Lomustine)?
Hepatotoxicity Dogs: 83-85% ALT elevation; 1.2-2.8% go into liver failure with this drug Cats: 6.8% ALT elevation; 0-3% go into liver failure Nephrotoxicity (rare, 12.2% have kidney issues in dogs in one study) Pulmonary fibrosis (cats with cumulative long-term dosing, rare)
What are unique side effects of doxorubicin?
Severe vesicant
Hypersensitivity/anaphylaxis (mast cell degranulation)
Cumulative cardiotoxicity in dogs (> 150-180 mg/m2)
Arrhythmogenic
Cumulative nephrotoxicity in cats (>140 mg/m2)
Doxorubicin-associated alopecia
What are unique side effects of hydroxurea?
Onchyomadesis
What are unique side effects of L-Asparaginase (Elspar, L-spar)?
Anaphylaxis
Pancreatitis
What are unique side effects of palladia?
Hypoalbuminemia PLN Hypertension Hepatopathy Muscle cramping Pancreatitis
What are the unique side effects of masitinib?
PLN
Hypertension
