Oncology - medical therapies Flashcards
What is chemotherapy?
Chemotherapy is genotoxic (i.e. damaging to DNA) treatment of disease by the use of chemical substances, especially the treatment of cancer by cytotoxic and other drugs
What does successful chemotherapy require?
– Standardised approaches
– Effective agents
– Multiple agents (usually)
– Multiple cycles
– A motivated client
– A patient with suitable demeanour
– A patient without factors pre-disposing to adverse effects
How is chemotherapy used?
- Primary chemotherapy. Chemotherapy is used as the sole anti-cancer treatment in sensitive tumour types
- Adjuvant Chemotherapy. Treatment is given after surgery to “mop up” metastatic (/microscopic residual) disease
- Neoadjuvant chemotherapy. Treatment is given before surgery to shrink tumour and increase chance of successful resection
- (Concurrent chemotherapy. Treatment is given simultaneous to radiation to increase sensitivity of cancer cells to RT)
What are principles of chemotherapy?
- Mainly active against rapidly proliferating tissues
- Does not specifically target cancer cells
– Cannot tell the difference between a cancer cell and a normal cell - Drugs may be cell cycle specific (thus targeting more rapidly dividing cells) or active at all stages
– Cells that are not actively dividing (those in G0) are relatively chemo resistant- act as a reservoir to repopulate the tumour
– Targets: DNA synthesis, RNA synthesis, protein synthesis, cell cycle progression - Chemotherapy is most effective against rapidly growing, highly proliferating tumours (high cell turnover, more likely to catch cells dividing)
- Drug resistance is a major cause of treatment failure in metastatic / disseminated disease and in this situation treatment is usually life extending rather then curative.
When is chemotherapy more likely to be effective?
- Earlier the better, when there is high tumour growth + few cells in G0
What are factors affecting chemotherapy success?
- Tumour cell heterogeneity (evolution of resistance) – linked to tumour size
- Inherent tumour sensitivity
– Origin tissue
– Growth fraction - Drug dosage
- Tumour blood supply/oxygenation
- Interval between treatments
How can you minimise drug resistance?
- Treat as early as possible
- Use standard protocols
- Use correct doses
- Administer agents properly
– Don’t pretreat lymphoma or mast cell tumour patients with steroids – causes resistance. Start at the same time as
chemo - At relapse, act ASAP
What should be considered when choosing a chemotherapy agent?
- Clinical situation
– What is the indication for chemotherapy
– What is the evidence of benefit of chemotherapy for that indication - Owner goals
– Chemotherapy is often palliative (longer or shorter term)
– Balance between QoL and treatment effect - Patient
– Signalment (may link to pharmacogenetic issues)
– ADME
– Co-morbidities - Dosing and scheduling
What are ADME factors affecting response + side effects?
- Administration
* Dose, ability to get into blood stream if oral - Distribution
* Ability of molecule to get to target site
* Size of drug, vasculature, necrosis, environment
* Blood barriers e.g. blood brain barrier
* Cellular uptake / efflux pumps e.g ABCB1 - Metabolism
* Drug activation / deactivation e.g. CYP450, glutathione s-
transferase
* (Anti-apoptotic mechanism, DNA damage repair) - Excretion
* Clearance – hepatobiliary system, kidney, (lung)
* For kidney excreted GFR correlates with adverse effects of some drugs
When would you use single agent chemotherapy?
- Used for exquisitely sensitive tumours
– Transmissible venereal tumour (TVT) - When second effective agent unknown
- Tends to select rapidly for drug resistance
– Selection pressure is high leading to rapid dominance of progeny of resistant cells.
What is the difference between sequential + combined polychemotherapy?
- Sequential
– Several drugs given at different times - Combined
– Several drugs given at the same time - Toxicity = combined>sequential
- Each agent should have different MoA + not interfere with each other
How to give chemotherapy?
- Route/rate depends on the drug
– Oral
– Intravenous = Bolus (rapidly) / Infusion (slowly)
– IM/SC
– Intracavitary - Try to avoid:
– Topical
– Intratumoural - Consider environmental contamination risk
What are patients that pose dosing problems?
- Obese patients – Should we be estimating lean weight?
- Collies and others with known drug sensitivity
– Test for MDR1 (ABCB1) mutations (Laboklin) - Animals with hepatic functional compromise
- Animals with reduced renal function
What should be done in a pre-chemotherapy assessment?
- Discuss tolerance of any previous treatment
- Assess patient
- Assess tumour status – For some tumours each time others periodic restaging
- Biochemistry
– Pre protocol
– Every few months
– Major unwellness - Haematology prior to each treatment
– Neutrophil > 3 x 109/L
– Platelets > 100 x 1010/L - Urinalysis start or treatment, prior to cyclophosphamide
What occurs if patient has immediate toxicity to chemo drugs (<24hrs)?
- Anaphylaxis/hypersensitivity – L-asparaginase (especially repeat doses), anthracyclines, cisplatin, cytosine
– IVFT, dex iv, H1 blocker, adrenaline - Cardiac arrhythmia – Doxorubicin (epirubicin)
- Emesis – Platinum compounds, actinomycin-D
