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
Mildly Myelosuppressive drugs
Vincristine (low dose)
Prednisone
L-asparaginase
Combination Chemotherapy goals
- Slow the onset of drug resistance
- Maximize tumor kill while minimizing toxicity
Approaches to combination chemotherapy
- Ideally chose agents for combination with differing targets or mechanisms of action
- Each drug should be effective against the tumor as a single agent
- Use agents/classes with reduced potential for cross resistance eg. alklyating agents and platinums
- Schedule dosing so toxicities do not overlap
> Combine myelosuppressive agents with those showing reduced myelosuppression
> eg. vincristine and cyclophosphamide - Use combinations supported by published data on efficacy and safety
