Chemotherapeutics and Immunotherapeutics Flashcards
What is chemotherapy?
systemic administration of chemical reagents that have specific toxic effects on neoplastic cells
Explain the steps of the cell cycle
G1 = growth (RNA/protein synthesis)
S = DNA synthesis
G2 = growth (RNA/protein synthesis)
M = mitosis
G0 = resting/non-dividing
- either the cell is post-mitotic and differentiated like a neuron or it has a lack of materials needed for mitosis
How does the cell cycle influence the efficacy of chemotherapeutics
The higher the growth fraction (faster the cell cycle) = the more chemosensitive the tumor is
the slower the cell cycle/low growth fraction = chemo is less effective
- ex. giant masses are usually slow growing and so chemotherapy is not that effective
What is the therapeutic index?
The ratio of the toxic dose to the anti-tumor dose
must balance host and tumor toxicity
What determines the therapeutic index when giving chemotherapeutics?
body surface area
- good estimate of metabolism
not body weight
What type of chemotherapy protocols are used? Why?
combination protocols given serially (not all at once)
able to target many aspect of the tumor = reduce risk of resistance
also multimodal treatment is better
- chemo + radiation + sx + immunotherapy
What considerations should you have when giving combination chemotherapy
use drugs with
- proven efficacy
- complimentary mechanisms of action
- balance toxicity
How are systemic chemotherapeutics administered
PO or IV
What are 2 main indications of use of systemic chemotherapeutics? Add examples of tumor types
depends on tumor type, some = more susceptible like…
- lymphoma*
- leukemia
- transmissible venereal tumor
adjuvant treatment for highly metastatic tumors
- canine osteosarcoma
- feline mammary carcinoma
used even when there isnt evidence of metastasis yet
Why is treating transmissible venereal tumor with chemotherapeutics unique?
because chemo can cure it!
What are contraindications for chemotherapy
treating a bulky tumor or local disease
- +/- shrink tumor pre-sx or palliative tx
- but not good evidence and reduced QoL
treating the owner - appeasing them
What are the basic principles to remember when introducing a patient to chemo
clearly define goals with owner
- so they understand why we are doing this
- so they have reasonable expectations (not curative)
patient evaluation (5 step approach)
- determine if ‘curative intent’ or palliative tx is most appropriate
What is curative intent therapy
designed to extend the length of life
not palliative
may require a reduce QoL for a period of time
What are the 5 steps to patient evaluation
- definitive histo diagnosis of malignancy (FnA can work but histo is better)
- accurate staging = diagnostics
- identify paraneoplastic effects (can impact prognosis/tx/QoL)
- identify any concurrant disease
- establish patient baseline
Differentiate grading and staging a tumor
grading: pathologist
staging: clinician
- series of diagnostics that evaluate how much cancer and where it is
What is the mechanism of antimetabolite chemotherapeutics
they are an analogue of metabolites needed to make nucleotides
they are incorporated in the synthesis (S) phase of the cell cycle but are actually non-functional
methotrexate/cytosine arabinoside/azathioprine
What is the mechanism of alkylating agents chemotherapeutics
They cause interstrand DNA binding
prevent separation of strands in M stage
cyclophosphamide/chlorambucil/melphalan
What is the mechanism of mitotic inhibitors chemotherapeutics
They bind microtubule proteins and cause mitotic arrest because the microtubules stop functioning and chromosome aren’t pulled apart
vincristine/vinblastine/taxol
What is the mechanism of antitumor antibiotics chemotherapeutics
They complex with DNA and from free radicals
doxorubican (adriamycin)/mitoxantrone
What is the mechanism of L-asparaginase? What is it used for mainly?
enzyme that degrades asparagine
it is a bit more specific to neoplastic cells because host cells deal better with reduced asparagine
lymphoma and some leukemia
What is the mechanism of platinum analoges
they covalently bind DNA
cisplatin/carboplatin
What is an example of targeted chemotherapy? What is its mechanism?
Palladia aka toceranib
It is a tyrosine kinase inhibitor
- mast cell tumors have mutated tyrosine kinase (c-kit)
- the drug will inhibit c-kit
How is screening used in targeted chemotherapy
you can screen for oncogenic mutations and use drugs that specifically target mutations
but sometimes not enough data/no drugs available
mainly for dogs (not cats)
Why is safety so important when working with chemotherapeutics?
they are mutagens/teratogens/carcinogens
How should you store chemotherapeutics
in labelled bins
specific storage
- refrigerator just for chemo drugs
What safety measures should be taken to prepare and administer chemotherapy
biosafety cabinats and respirators
PPE -
- talc-free gloves
- impermeable gown
- face shield
use closed system drug transfer devices
administer in a quiet and isolated area with good restraint
- aseptically place the catheter
What are important things to note about patient care post-chemo in the hospital and at home?
in hospital
- use gloved when handling body waste
- mop areas with disposable sponge
- appropriate disposal of contaminated items
home
- highest drug residues after 72h
- gloves when handling waste
- no kisses/face licking
- isolated poop area
What are immunotherapeutics
drugs used to treat injury due to immune mediated or inflammatory disease
List some examples in which immunotherapy can be used
skin disease
inflmmatory bowel disease
glomerulonephritis
immune mediates (IMHA/thrombocytopenia/polyarthropathy)
neuro (nonsuppurative meningitis/myesthenia gravis)
neoplasm( lymphoma/leukemia/mast cell tumor)
What are glucocorticoids used for in dogs and cats
immune mediated disease
What are the mechanisms of action of glucocortioids
reduce cytokine and immune mediator production
reduce macrophage activity
lympholytic
reduce complement
reduce migration of neutrophils
reduce Ig production
What are the prod of using glucocorticoids
broad efficacy
available
increase QoL
What are the cons of glucocorticoids
overprescribed in dose and length of admin
iatrogenic cushings
increase weight
increase risk of
- diabetes mellitus/insulin resistance
- opportunisitic infection
hypertension/destabalize cardiovascular function
proteinuria
calcinosis cutis
dogs have worse adverse effects
What is calcinosis cutis
dogs
ulceration and mineralization in skin after prolonged glucocorticoid administration
How to optimize glucocorticoid use
use lowest dose/shortest course possible
taper dose/frequency
use in combo with other immunotherapies
- allow for a lower dose to be used
What is an example of a main glucocorticoid used
cyclosporine
aka atopica
What is the mechanism of cyclosporine
inhibit T cells
potent
What are the pharmacokinetics of cyclosporine
reduced absorption if there is food in the small intestine
lots of drug interactions because it interacts with CYP450
can monitor with whole blood
What are the acute and chronic adverse effects of cyclosporine? What is a contraindication
acute
- vomit
- diarrhea
- anorexia
- lethargy
chronic
- secondary infection
- increase neoplasia risk
dont use if there is a concurrant neoplastic disease
What is best practice for administering glucocorticoids
frequent rechecks
taper and monitor
safe drug handling
