Chemotherapy 2 Flashcards
Cisplatin, carboplatin
- type of drugs
- what are they? how they work?
- comparison?
Platinums, chemotherapeutics
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- Heavy metal (platinum) containing agents
- Cytotoxic due to DNA alkylation (cross linking effects)
- Carboplatin is less potent than cisplatin; has a similar spectrum of activity
Cisplatin, carboplatin
- elimination? toxic effects? how to avoid?
- contraindications?
- adverse effects?
Platinums are largely eliminated by kidneys
- Cisplatin is highly nephrotoxic in dogs
> Fluid loading before and after treatment reduces renal effects
> Carboplatin is less nephrotoxic
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- Cisplatin contraindicated in cats due to pulmonary complications; acute fatal edema possible
> Carboplatin may be used in cats
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- Vomiting common with cisplatin, but not carboplatin
Platinums - used to treat what?
Used to treat solid tumors
- Osteosarcoma and other carcinomas
- Cisplatin also given intracavitary in some cases - Intralesional use in dogs, cats and horses
> Cisplatin for sarcoids in the horse
> Carboplatin-oil emulsion in cats; nasal SCC
Vincristine, Vinblastine
- type of drugs
- where they derive from
- what they do?
- use?
- comparison?
- adverse effects?
Vinca alkaloids; plant (periwinkle) derivatives
- Bind tubulin; inhibit mitotic spindle assembly
- Vinblastine can also block purine synthesis
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Both are used to treat lymphoma; vincristine is used over vinblastine
- Also used in lymphoid leukemias
- Usually used in combination therapy
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- Vincristine is effective for canine TVT
- Vinblastine is most used in canine mast cell tumors
- Vinblastine generally used less commonly than vincristine due to significant myelosuppression compared to vincristine
- Extravasation reactions possible with both agents
- Neurotoxicity in humans has been noted due to accumulation of drug
Antimetabolite chemotherapeutic drugs
Methotrexate, Cytosine arabinoside
Methotrexate
- what is it?
- mechanism?
- use?
- adverse effects?
- antidote? how it works?
- elimination?
Antimetabolite chemotherapeutic drugs
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- Inhibits enzymes ie. dihydrofolate reductase required for folate production
> inhibition of purine nucleotide synthesis ̈ Use limited to lymphoma protocols
- Gastrointestinal toxicity most common
- Leucovorin is an antidote for methotrexate toxicity
> Provides alternative source of folate for cells
> Used empirically in humans with high dose methotrexate regimens
- Eliminated primarily by the kidney
Cytosine arabinoside
- what is it?
- mechanism
- goes where?
- use?
Antimetabolite chemotherapeutic drugs
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- Converted to cytarabine triphosphate inside cells; inhibits DNA polymerase and DNA synthesis
- Crosses into CNS easily when given parenterally
> Used for lymphoma including CNS lymphoma
> Also leukemias and meningioencephalomyelitis of unknown etiology
L-Asparaginase
- type of drug
- where it comes from
- mechanism
- use?
- adverse effects?
Enzyme chemotherapeutics
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- An enzyme derived from E.coli
- Breaks down asparagine to aspartic acid and ammonia
> Some tumor cells unable to produce asparagine; rely on extracellular source
- Asparagine important for DNA, RNA and protein synthesis
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Used primarily in lymphoma protocols
- Used primarily to induce remission, with less use in maintenance protocols due to rapid resistance
- Use in lymphoid leukemia and mast cell tumor has been suggested
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The most common adverse effect in humans is
hypersensitivity (allergic) reactions
- may develop from repeated administrations
- Less common in veterinary patients
> Has minimal effect on bone marrow
Toceranib Phosphate
- type of drug
- mechanism
- license? dose form?
- adverse effects?
Tyrosine Kinase Inhibitor chemotherapeutic
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- A multi-kinase inhibitor targeting several receptor tyrosine kinases > C-KIT, PDGF, VEGF
- Has antitumor and antiangiogenic effects
- Antiproliferative effect on endothelial cells
- Can induce apoptosis in tumor cells
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Licensed for use in canine mast cell tumors
- Available as oral tablets (do not split)
> Use gloves if tablet spit out by dog
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The most common adverse effect in dogs is anorexia, vomiting and diarrhea; GI perforation possible
- Moderate neutropenia noted
- Thrombocytopenia can occur
- Can cause vascular dysfunction and thromboemboli formation
- CYP450 inhibitors can increase Toceranib levels
Corticosteroids used as chemotherapeutics
Prednisolone, Dexamethasone
Prednisolone, Dexamethasone use as chemotherapeutics
- what they do?
- uses?
- adverse effects?
Direct cytoxicity in lymphoma
- Also used in lymphoid leukemia, mast cell tumors and some brain tumors
- Primarily used in combination protocols as resistance develops rapidly
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Symptomatic support in several tumor types
- Mast cell tumor
> Reduces inflammation, edema
> Reduced movement of eosinophils, neutrophils
- Space occupying tumors; relieves compression by shrinking tumor
- Antiinflammatory effects may provide pain relief
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Stimulates appetite and attitude
- Euphoria and improved quality of life ??
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Potential for adverse effects
- PU/PD
- Gastrointestinal ulcers
- Susceptibility to infections
most common dose- limiting toxicity with antineoplastics
Myelosuppression and infection
- Endogenous bacterial infections from normal flora
> GI tract: gram negative aerobes and anaerobes
> Skin: Staphylococcus
> Catheter related bacteremia’s
Myelosuppression - why it occurs with chemotherapeutics?
- when do we see the nadir? why? what is this?
- nadir significance?
- what -penias do we observe?
High growth rate of bone marrow cells
- Proliferating hematopoietic progenitor and precursor cells most susceptible to cytotoxicity
> Non-proliferating stem cells more resistant
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More differentiated nonproliferating mature hematopoietic cells yields neutrophils for ~5-10 days
- Nadir (low point) follows; usually lasts a few days
- Nadir dictates dosing interval with agents
> usually every 3-4 weeks
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Neutropenia then thrombocytopenia; rarely anemia
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Monitor absolute neutrophil counts regularly
- Low counts (<1000 cells/μL)
> May require prophylactic antibiotics
> Reduce subsequent doses of drug
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rhG-CSF may be indicated in severe neutropenia
Highly Myelosuppressive drugs
Doxorubicin
Vinblastine
Cyclophosphamide
Carboplatin
Mitoxantrone
Moderately Myelosuppressive drugs
Melphalan
Vincristine (high dose)
Methotrexate
Cisplatin
Chlorambucil
Toceranib
