Oncology: Medical Therapies Flashcards
What is chemotherapy?
Chemotherapy is genotoxic treatment of disease by the use of chemical substances
What are the different applications of chemotherapy?
- Primary- sole- anticancer treatment
- Adjuvant- after surgery ‘mop up’
- Neoadjuvant chemotherapy- beofre surgery to shrink
- Concurrent- with radiation to increase sensitivity of RT
- What cells does chemo target?
- How can cells act as reservoirs?
- What are the targets of chemo?
- Highly proliferating tissues
- Cells in G0 can repopulate
- DNA synthesis, RNA synthesis, protein synthesis, cell cycle progression
When is chemotherapy most and least effective?
What is the major cause of chemotherapy failure?
- Most effective against rapidly dividing cells
- Slow growing (indolent) typically resistant
Drug resistance casues failure
At which stage is chemotherapy most likely to be effective?
C- fast growing, smallest
How are tumours heterogenous?
- Cancer is a result of genetic instability- leads to more varitaion
- As they progress they become ‘subclones’
- Therefore may be lots slightly different
What factors affect chemotherapy success?
- Growth fraction and mass doubling time
- Tumour cell heterogeneity
- Inherent tumour sensitivity
- Drug dosage
- Tumour blood supply/oxygenation
- Interval between treatments
How can drug resistance be minimised?
- Treat as early as possible
- Use standard protocols
- Use correct doses
- Administer agenst properly
- At relapse act ASAP
What tumours should not be pre-treated with steroids?
Lymphoma or mast cells
Causes resistance
What factors influence choice of chemotherapy agents?
- Clinical situation- indication, evidence of benefit
- Owner goals- often palliative, balance between QoL and effect
- Patient- signlamnet, co-morb
- Dosing and schedule
What affects response and side effects of chemotherapy?
- Administration- dose ability to enter blood if oral
- Distribution- target site, cellular uptake (BBB, vasculature)
- Metabolism- drug activation
- Excretion- clearance
What tumour can recieve single agent chemotherapy?
Transmissible venereal tumour
How can polychemotherapy be achieved?
Sequential- several drugs at different times
Combined- several drugs at same time
With polychemotherapy what should they achieve together?
What should be avoided?
Should
* Have proven efficacy
* Different modes of action
* Affect different stages of cell cycle
* non-overlapping dose limiting toxicities
* not interfere
Should avoid
* Arbitrarily exclude one of the drugs from protocol
* Reduce drug dose
What routes of chemotherapy should be avoided?
- Topical
- Intratumoural
When can patients pose dosing problems?
- Obese patients
- Collies with drug sensitivities
- Hepatic function compromise
- Reduced renal function
Why is dosing rate difficult?
High dose chemo has a narrow therapeutic window
Too low- ineffective
Too high- toxic
When should chemotherapy dose be reduced?
Only lower as needed based on actual adverse effects
What is the purpose of dose density?
- Designed to allow recovery of normal tissues
- Rapidly dividing tissue such as bone marrow and GI tract have tremendous capacity to repair rapidly
What is the common first line chemotherapy protocol for a canine lymphoma?
CHOP
* vincristine, doxorubicin, cyclophosphamide, prednisolone
CEOP
* vincristine, epirubicin, cycloposphamide and prednisolone
What is the common first line chemotherapy protocol for lymphoma in cats?
high dose COP
* vincristine, cyclophosphamide and prednisolone
What should be assessed before chemotherapy?
- Tolerance of previous treatment
- Assess patient
- Assess tumour status
- Biochemistry- pre-protocol, every few months
- Haematology prior to treatment
- Urinalysis
What chemotherapy planning needs to take place?
- Risks and benefits with owner
- Ensure- not pregnent, no very young children
- Practice is sufficient to administer drugs safely
- Appropriate PPE is available
- Written owner info
Prior to each chemotherapy treatment what do neutrophils and platlets need to be?
Neutrophils over 3 x 10^9/L
Platelets over 100 x 10^10/L
What can occur with immediate toxicity?
- Anaphylaxis
- Cardiac arrythmia
- Emesis
What is acute tumour lysis syndrome?
How does it show?
How is it managed?
When large tumour burdent are rapidly destroyed- lymphoma
Acute kidney injury, electrolyte abnormalities
Early IVFT, managment of AKI
What are the general side effects of chemotherapy?
BAG
* Bone marrow- low WBC 7-10 days
* Alopecia- uncommon in dogs/cats
* GI- not after first 4 days
What causes GI toxicity
What can it cause?
What can the sequale be?
Direct damage to enterocytes
Anorexia, nausea, vomiting, diarrhoea
Disrupted musocal barrier increases risk of sepsis
How is GI toxicity managed?
Pre-emptive home managment
* Maropitant
* Pre-treatment fasting
* Consider smectite
Supportive treatment for severe cases (prolonged/unwell)
How can toxicity be caused 7-10 days post chemo?
How is it treated?
Damage to emerging haematopoetic cells
* dip in neutrophil counts, too low leads to risk of sepsis
Hospitalise until systemically well
Stop cytotoxic drugs
Supportive
If neutrophils low- ABs, dose reduction
What are possible drug associated complications?
- Cumulative cardiotoxicity- doxorubicin
- Sterile haemorrhagic cystitis- cyclophosphamide : tx- furosemide
- Hepatotoxicity- Lomustine
- Nephrotoxicity- cisplatin, doxorubicin (cats)
- Peripheral neuropathy- vincrisitne
- Non-cadiogenic pulmonaty oedema- cisplatin (cats)
- Fatal CNS signs-
What does this image show?
What about chemo can cause this?
Extravasation of drugs
Very irritant
Doxorubicin, epirubicin
Vincristine/vinblastine
Catheter- Flush before removal
How are extravasations treated?
- If suspected- do not flush
- Doxorubicin- apply cold packs, topical DMSO, consider surgical debridement
- Vincristine- apply warm, compress, topical DMSO, hyaluronidase
- What is metronomic chemotherapy?
- What is its main target?
- How is it often applied?
- Continuous low dose chemotherapy
- Angiogenesis
- Usually pallitavely or after MTD chemo
What drugs are generally given for metronomic chemotherapy?
Low dose
Cyclophosphamide with piroxicam
What is the action of tyrosine kinase inhibitors?
Inhibit the activation of specific signalling pathways involved in specific types of cancer
What can tyrosine kinase inhibitors also effect?
Effect on angiogenesis
Toxicity
Need regular monitoring
Diarrhoea, vomiting, anorexia
Bone marrow suppression
