Oncology 3 Flashcards
General principles of chemotherapy.
- Owner factors.
- Patient factors.
- Indications.
- Dose and timing.
- Drug resistance.
- Safe handling.
- Toxicity.
- Give some examples of patient factors.
- Give some examples of owner factors.
- Age. current health, current med, allergies, temperament.
- Owner ability to care, cost, owner current health, pregnancy.
What are indications for chemotherapy?
- Chemo-sensitive tumours.
- Often used as primary therapy for haemopoietic malignancies e.g. lymphoma.
- As adjunctive therapy e.g. following surgery, for solid tumours – eradicates or manages metastatic disease.
Why do we not use chemotherapy for treatment of solid tumours?
Most chemotherapeutic agents act upon processes in cell growth and division e.g. DNA replication, mitotic spindle.
– Rapidly dividing cells most susceptible, and those in resting phase of cell cycle (G0) are most resistant.
–> These G0 cells can act as ‘reservoir cells’ that can re-populate unless there is complete surgical excision.
- Ideally use chemo when growth fraction is at its highest e.g. early in disease process or after debulking.
Why is dosing and timing of chemo so important?
To work, chemo drug must reach the cancerous cells, exert a cytotoxic effect within the cell and resistance must not develop.
What are the determining factors for the drug reaching the cancerous cells, exerting cytotoxic effect and not allowing resistance to develop?
Whether a single or multiple agents used.
Drug(s) given and the mech of action.
Dose.
Timing of administration.
- Pros of single agent chemo.
- Cons of single agent chemo.
- Decreased cost.
- Decreased risk of toxicity.
- Decreased time in hospital.
- Decreased cost.
- Decreased efficacy.
- Drug resistance develops faster.
- Decreased efficacy.
- Pros of multiple agent chemo.
- Cons of multiple agent chemo.
- Greater efficacy.
- Drug resistance develops slower.
- Greater efficacy.
- Increased cost.
- Increased risk of toxicity.
- Increased time spent in hospital.
- Increased cost.
Platinum compounds…
1. MoA.
2. Examples.
3. Example uses.
- Cross-linking and damaging DNA, inhibiting replication.
- Cisplatin, carboplatin.
- Osteosarcoma.
Alkylating agents…
1. MoA.
2. Examples.
3. Example uses.
- Cross-links DNA, inhibiting replication and transcription.
- Cyclophosphamide, lomustine, chlorambucil.
- Lymphoma, multiple myeloma.
Anti-metabolites…
1. MoA.
2. Examples.
3. Example uses.
- Inhibit use of cellular metabolites during growth/division.
- Cytarabine, azathioprine, methotrexate.
- Lymphoma and leukaemia.
Anti-tumour antibiotics…
1. MoA.
2. Example.
3. Example use.
- Several.
Incl. promotion of free radicals and inhibition of enzymes required for DNA replication. - Doxorubicin.
- Lymphoma.
Tyrosine kinas inhibitors…
1. MoA.
2. Examples.
3. Example uses.
- Inhibit tyrosine kinase, which when activated, leads to aberrant cell growth. Used to treat tumours expressing c-kit mutation.
- Masitinib, toceranib.
- MCTs, GI stromal tumours.
Enzyme…
1. MoA.
2. Example.
3. Example use.
- Destroys circulating asparagine necessary for protein synthesis.
- L-asparaginase.
- Lymphoma.
Plant alkaloids…
1. MoA.
2. Examples.
3. Example uses.
- Disable mitotic spindle.
- Vincristine and vinblastine.
- Lymphoma and MCT.
NSAIDs…
1. MoA.
2. Examples.
3. Example uses.
- Induce apoptosis.
- Piroxicam, Meloxicam.
- Transitional cell carcinoma, colonic adenocarcinoma.
Glucocorticoids…
1. MoA.
2. Example.
3. Example use.
- Cytotoxic to lymphocytes and decrease lymphocyte proliferation.
- Prednisolone.
- Lymphoma.
Immunotherapy…
1. MoA.
2. Example.
3. Example uses.
- Causes antibody production that cross react w/ canine tyrosinase which is essential for melanin synthesis.
- Melanoma vac.
- Digit and oral melanoma.
What is the purpose of combining chemo drug classes?
To increase efficacy of treatment whilst helping to avoid side effects.
This helps balance effective dosing with causing limited harm.
What areas of the body are most commonly affected by chemo and why?
Bone marrow and gut epithelium – rapidly dividing cells here.
- By which order kinetics do chemotherapeutics act?
- First order. – kill a fixed percentage of cells opposed to set number.
What factors of timing affect treatment outcome?
Promptness of beginning treatment and regularity of treatment.
- Primary drug resistance.
- Secondary drug resistance.
- Cancer resistant to drug in the first place.
- Develops due to mutation and selection of resistant clones.
- With what aim may prednisolone be prescribed?
- Downfall of pre-treatment preds?
- Palliative care before definitive dx.
A light touch chemo option for some cancers e.g. lymphoma. - Helps drug resistance to develop more swiftly. – may be due to increased expression of proteins with multi-drug resistance potential e.g. MDR-1. –> codes for production of a protein called ‘p-glycoprotein’ which is able to pump some chemotherapeutic drugs out of cell.
