ONCOLOGY - Chemotherapy Flashcards
What are the aims of chemotherapy in veterinary medicine?
Prolong survival
Maintain a good quality of life
Minimise side effects
What should be done prior to proceeding with chemotherapy?
- Confirm diagnosis of neoplasia
- Clinically stage the neoplasia
- Stabilise paraneoplastic syndromes
- Treat concurrent disease
Why are haematopoietic tumours so chemosensitive?
Haematopoietic tumours are so chemosensitive due to the high rate of cell division seen with this neoplasia
Why are sarcomas and carcinomas so chemoresistant?
Sarcomas and carcinomas are chemoresistant due to their low rate of cell division
What is conventional chemotherapy?
Conventional chemotherapy is the use of cytotoxic drugs which have a non-specific effect on all rapidly dividing cells in the body
What is the maximum tolerated dose (MTD)?
The maximum tolerated dose (MTD) is the maximum dose of conventional chemotherapy that can be administered without causing severe toxicity or unacceptable side effects
In which phase of the cell cycle are cells resistant to chemotherapy?
G0 phase of the cell cycle
Which chemotherapy drug classification targets the M phase of the cell cycle?
Vinca alkaloids
What is the mechanism of action of the vinca alkaloids?
Vinca alkaloids inhibit the mitotic spindle resulting in the prevention of the chromosomes being pulled apart during metaphase, resulting in metaphase arrest and cell death
Give two examples of vinca alkaloids
Vincristine (oncovin)
Vinblastine
Which specific side affects are associated with vinca alkaloids?
Neurotoxicity
Neuropathies
Which chemotherapy drug classification targets the S phase of the cell cycle?
Antimetabolites
What is the mechanism of action of the antimetabolites?
Antimetabolites intefere with DNA replication and protein synthesis through mimicking essential molecules such as pyrines and pyramidines, resulting in the antimetabolites becoming incorporated into the genetic material, disrupting DNA replication and protein synthesis, resulting in cell death
Give two examples of antimetabolites
Rabacfosadine
Hydroxyurea
What is the specific side effect associated with rabacfosadine?
Pulmonary fibrosis
List three classifications of cell cycle phase non-specific chemotherapy drugs
Alkylating agents
Antitumour antibiotics
Miscellaneous chemotherapy drugs
What is the mechanism of action for alkylating agents?
Alkylating agents contain an alkyl group that can bind to DNA resulting in inter- and intrastrand cross-linking which will impair DNA replication resulting in cell death
List four examples of alkylating agents
Cyclophosphamide
Melphanan
Chlorambucil
Lomustine
Which specific side affect is associated with cyclophosphamide?
Haemorrhagic cystitis
How does cyclophosphamide cause haemorrhagic cystitis?
When cyclophosphamide is metabolised by the liver, one of the metabolites produced is acrolein. When acrolein comes into contact with the bladder wall, this can cause inflammation and haemorrhagic cystitis
What is the consequence of untreated haemorrhagic cystitis secondary to cyclophosphamide administration?
Chronic fibrosis of the bladder wall
How do you treat haemorrhagic cystitis due to cyclophosphamide?
Stop administering the cyclophosphamide
Antibiotics if identify secondary infection on urine culture
Substitute cyclophosphamide
Which two alkylating agents can be used to substitute cyclophosphamide?
Chlorambucil
Melphanan
How do you prevent haemorrhagic cystitis due to cyclophosphamide?
Give cyclophosphamide in the morning
Encourage drinking and urination (prednisolone helps with this)
Furosemide if administering cyclophosphamide without prednisolone
Monitor for haematuria on urine dipstick
What are the three mechanisms of action for antitumour antibiotics?
Directly inhibit DNA replication and protein synthesis
Inhibit topoisomerase enzyme
Produce free radicals
List two examples of antitumour antibiotics
Doxorubicin
Actinomycin D
Which specific side effects are associated with doxorubicin?
Cardiotoxicity
Nephrotoxicity
Hypersensitivity
What are the acute cardiotoxic affects of doxorubicin?
Arrhythmias
What are the chronic cadiotoxic affects of doxorubicin?
Myocytolysis
Myofibre swelling
Cardiac fibrosis
Secondary dilated cardiomyopathy
How many doses of doxorubicin can be administered relatively safely?
Six doses
What can be done to prevent doxorubicin cardiotoxicity?
Assess cardiac function on echocardiography prior to beginning treatment
Do not exceed to cumulative dose of 180mg/m2
Substitute doxorubicin with another chemotherapy drug
Administer doxorubicin slowly IV over 20 minutes
Which chemotherapy drugs can be used as an alternative to doxorubicin?
Epirubicin
Mitoxantrone
List two of the miscellaneous chemotherapy drugs
L-asparaginase
Cisplatin
What is the mechanism of action for L-asparaginase?
L-asparaginase depletes the levels of the amino acid asparagine within the body. Neoplastic cells cannot produce their own asparagine and thus require endogenous asparagine for survival. Depleting asparagine leads to the death of cancer cells
Which specific side effect is associated with L-asparaginase?
Hypersensitivity
What are the clinical signs of the hypersensitivity reactions seen with doxorubicin and L-aspariginase?
Vomiting
Restlessness
Pruritis
Wheals
Oedema
Dyspnoea (cats)
How do you treat hypersensitivity reactions due to L-aspariginase?
Slow administration of the drugs
Intravenous fluids
Antihistamine
Dexamethasone
Adrenaline
How do you prevent hypersensitivity reactions due to doxorubicin and L-asparaginase?
Antihistamine pretreatments
Ensure correct route of administration
Administer doxorubicin slowly IV over 20 minutes
What are the correct routes of administration for L-aspariginase?
Subcutaenous
Intramuscular
Which specific side effect is associated with cisplatin?
Nephrotoxicity
Which drug can be used as an alternative to cisplatin?
Carboplatin
Why is prednisolone often incorporated into chemotherapy protocols?
Prednisolone is used to reduce inflammation and promote appetite while a patient is on chemotherpay in order to improve quality of life
What are the general side effects of chemotherapy?
Myelosuppression
Alopecia
Gastrointestinal distrubances
What are the consequences of myelosuppression?
Anaemia
Thrombocytopenia
Neutropenia
What are the generalised delayed side effects of chemotherapy?
Infertility
New tumour formation
Why is it so important to administer intravenous (IV) chemotherapy correctly?
Incorrect administration of intravenous (IV) chemotherapy drugs can lead to perivascular reactions
When carrying out chemotherapy, which factors should you assess at every visit?
1. Is the patient responding to the chemotherapy? If yes then continue the chemotherapy, if no, either increase the doses or change the protocol
2. Is the patient well with no unacceptable side effects? If yes then continue the chemotherapy, if no, either decrease the dose, provide symptomatic treatment, change the protocol or stop the chemotherapy
What should you do to determine if the patient is responding to the chemotherapy?
Thorough history
Thorough clinical examination
Necessary blood work and diagnostic imaging
What should you do to determine if the patient is well with no unacceptable side effects to the chemotherapy?
Thorough history
Thorough clinical examination
Identify and grade any side affects
How do you treat lymphoma?
- Stabilise paraneoplastic syndromes (hypercalcaemia)
- Treat concurrent disease
- Chemotherapy
What are the three main chemotherapy protocols used for lymphoma?
COP
CHOP
CLOP
COP is less toxic than CHOP
What are the components of the COP protocol?
Cyclophosphamide
Oncovin (vincristine)
Prednisolone
How do you carry out the induction phase of the low dose COP protocol?
Adminster weekly high dose IV vincristine injections, oral cyclophosphamide every 48 hours, and prednisolone every 24 hours for 7 days before reducing the dose and administering prednisolone every 48 hours, for 6 - 8 weeks. If the patient is in complete remission within 6 - 8 weeks, begin the maintenance phase
What should you do if a patient is not in complete remission following the induction phase of the low dose COP protocol?
If the patient is in partial remission or has stable disease after the induction phase, continue high dose administration or change the chemotherapy protocol
How do you carry out the maintenance phase of the low dose COP protocol?
Administer the chemotherapy protocol on alternate weeks for up to 2 years. At 6 months, change cyclophosphamide to chlorambucil to reduce the risk of haemorrhagic cystitis
What should you monitor during the low dose COP protocol?
Haematology
Urinalysis
Why should you monitor haematology during the low dose COP protocol?
Monitor haematology to determine the degree of neutropenia
How often should you monitor haematology during the low dose COP protocol?
Baseline values prior to beginning chemotherapy
Monthly unless patient presents with pyrexia or is generally unwell
Why should you monitor urinalysis during the low dose COP protocol?
Monitor urinalysis for any haematuria which could indicate haemorrhagic cystitis
How often should you do urinalysis during the low dose COP protocol?
Baseline values prior to beginning chemotherapy
Weekly urine dipsticks
Monthly full urinalysis
How do you carry out the induction phase of the high dose COP protocol?
Administer weekly high dose IV vincristine injections for the first 3 doses, and then reduce the frequency to every three weeks. Adminster three weekly IV cyclophosphamide injections, and oral prednisolone every 24 hours for 28 days and then every 48 hours. If the patient is in complete remission at 6 - 8 weeks, begin the maintenance phase
How do you carry out the maintenance phase of the high dose COP protocol?
At 6 months, increase the adminstration cycle to every 4 weeks. At 12 months, increase the administration cycle to every 5 weeks and at 18 months, increase the administration cycle to every 6 weeks
When is the high dose COP protocol particularly useful?
High dose COP protocol is particularly useful in cats where tablets can be challenging to dose and administer frequently or with owners who want fewer visits to the practice
What are the components of the CHOP protocol?
Cyclophosphamide
Hydroxydaunorubicin (Doxorubicin)
Oncovin (Vincristine)
Prednisolone
How do you carry out the induction phase of the CHOP protocol?
The induction phase of the CHOP protocol is carried out over two weeks, with two cycles of vincristine, cyclophosphamide, vincristine, doxorubicin and no treatment. For the first week, also administer weekly prednisolone injections, reducing the dose every time. You can also include L-aspariginase but this is optional. If the patient is in complete remission by the end of the 10 weeks, begin the maintenance phase
How do you carry out the maintenance phase of the CHOP protocol?
Repeat the two cycles of drug administration with two weeks between each drug dose. In total this will take 25 weeks
What should you monitor during the CHOP protocol?
Haematology
Urinalysis
Echocardiography
Why should you monitor haematology during the CHOP protocol?
Monitor haematology to determine the degree of neutropenia
How often should you monitor haematology during the CHOP protocol?
Baseline values before beginning chemotherapy
Weekly
Why should you monitor urinalysis during the CHOP protocol?
Monitor urinalysis for any haematuria which could indicate haemorrhagic cystitis
How often should you do urinalysis during the CHOP protocol?
Baseline values before beginning chemotherapy
Prior to and after every cyclophosphamide administration
How often should you do echocardiography during the CHOP protocol?
Baseline before beginning chemotherapy
At the fourth dose of doxorubicin
What are the components of the CLOP protocol?
Cyclophosphamide
Lomustine
Oncovin (Vincristine)
Prednisolone
When is the CLOP protocol indicated?
The CLOP protocol is indicated for high grade large T cell lymphoma
Why is it so important to do haematology when prior to every chemotherapy administration?
It is very important to do a haematology when assessing patients on chemotherapy to assess the effects of myelosuppression, including neutropenia, anaemia and thrombocytopenia. The haematology results can influence if chemotherapy should go ahead or not that day
What is the normal reference range for neutrophils?
3 - 12x10^9
What is a mild neutropenia?
2 - 2.5x10^9
How should you alter your chemotherapy protocol if a patient presents with a mild neuropenia?
Decrease the chemotherapy drug doses by 10 - 25% or delay further treatment until the neutrophil values have increased
What is a moderate neutropenia?
0.75 - 2x10^9
How should you alter your chemotherapy protocol if a patient presents with a moderate neuropenia?
If the patient is not pyrexic, stop the chemotherapy and monitor closely. If the patient is pyrexic, stop the chemotherapy and beging antibiotics ± IV fluids
What is a severe neutropenia?
Less than 0.75x10^9
How should you alter your chemotherapy protocol if a patient presents with a severe neuropenia?
Stop chemotherapy and begin IV antibiotics and IV fluids
How do you manage the gastrointestinal side effects of chemotherapy?
Treat symptomatically with antiemetics, antidiarrhoeals, gastroprotectants and IV fluids if indicated. Stop chemotherapy temporarily if the patient is presenting with severe gastrointestinal signs and allow them to recover before proceeding
How do you manage the alopecia due to chemotherapy?
Discourage owners from bathing or clipping the patient as this can encourage hair loss
What is acute tumour lysis syndrome?
Acute tumour lysis syndrome is the effect of the acute lysis of neoplastic cells in the first week of chemotherapy where the neoplastic cell burden is at it’s highest. This results in the mass release of intracellular components resulting in hyperkalaemia, hyperphosphataemia, hypocalcaemia, uric acid production and metabolic acidosis
What are the clinical signs of acute tumour lysis syndrome?
Acute lethargy
Bradycardia
Vomiting
Diarrhoea
Shock
How do you manage acute tumour lysis syndrome?
Intravenous fluids
Symptomatic treatment
Why is the expression of p-glycoprotein p170 of such concern in terms of chemotherapy drug resistance?
The expression of p170 allows for the efflux of chemotherapy drugs from cancerous cells which can result in multi-drug resistance
Which classifications of chemotherapy drugs are affected by multidrug resistance?
Vinca alkaloids
Antitumour antibiotics
Which classifications of chemotherapy drugs are not affected by multidrug resistance?
Alkylating agents
Carboplatin
What is the most common cause of neoplastic relapse?
Multi-drug resistance due to the expression of the p170 glycoprotein
How can you manage neoplastic relapse?
Start induction phase again
Use single agent chemotherapy drugs
Use another chemotherapy protocol
How do you treat acute lymphoid (lymphoblastic) leukaemia?
Acute lymphoid (lymphoblastic) leukaemia is very similar to high grade lymphoma and thus you can use the same chemotherapy protocols as used for lymphoma, such as COP and CHOP. However be aware the prognosis is poor for acute lymphoid leukaemia
How do you treat chronic lymphoid (lymphocytic) leukaemia?
In mild cases, chronic lymphoid (lymphocytic) leukaemia does not require treatment. However, in cases that do require treatment, chlorambucil and prednisolone are used
How do you treat acute myeloid leukaemia?
Acute myeloid leukaemia has a very poor prognosis and has no established chemotherapy protocol
How do you treat chronic (granulocytic) myeloid leukaemia?
Single agent chemotherapy protocol using Hydroxyurea
How do you treat multiple myeloma?
- Stabilise paraneoplastic sydromes (hypercalcaemia and hyperviscosity syndrome)
- Treat secondary infections
- Treat concurrent disease
- Chemotherapy
Which chemotherapy protocol is used for multiple myeloma?
Melphanan
Prednisolone
What is the prognosis for multiple myeloma with chemotherapy?
Good prognosis if the patient does not have hyperviscosity syndrome
How should chemoresistant tumours be treated (such as sarcomas and carcinomas)?
For chemoresistant tumours, cytoreductive surgery can be used to excise as much as the tumour as possible followed by chemotherapy to kill any residual primary tumour cells and to delay the growth of subclinical metastases
What are haemangiosarcomas?
Haemangiosarcomas are tumours which typically originate at the spleen and rapidly metastasise to the lungs
How do you treat a haemangiosarcoma?
Splenectomy to remove the primary tumour, followed by single agent doxorubicin chemotherapy to delay metastasis, or metronomic chemotherapy with cyclophosphamide and NSAIDS
What is the prognosis for a haemangiosarcoma with surgery alone?
1 - 3 months
What is the prognosis for a haemangiosarcoma with surgery and chemotherapy?
5 - 7 months
What are osteosarcomas?
Osteosarcomas are tumours which originate in the bone and rapidly metastasise to the lungs
How do you treat an osteosarcoma?
Amputation to remove the primary tumour, followed by single agent carboplatin chemotherapy to delay metastasis
What is the prognosis for an osteosarcoma with no treatment?
1 month
What is the prognosis for an osteosarcoma with amputation alone?
3 - 4 months
What is the prognosis for an osteosarcoma with amputation and chemotherapy?
10 months
What is metronomic chemotherapy?
Metronomic chemotherapy is the daily administration of chemotherapy drugs at low doses, typically administered by anti-angiogenic drugs such as NSAIDS
What are the benefits of metronomic chemotherapy?
Reduced risk of side effects
May be immunomodulatory
May targer dormant cells and neoplastic stem cells, preventing tumour repopulation
Which chemotherapy drugs can be used metronomically?
Alkylating agents
Tyrosine kinase inhibitors
What is targeted chemotherapy?
Targeted chemotherapy is the use of drugs which specifically target critical molecular structures/signalling pathways associated with specific cancer cells. Some of these drugs can also be anti-angiogenic
What is the main classification of targeted chemotherapy drugs?
Tyrosine kinase inhibitors (TKIs)
List three examples of tyrosine kinase inhibitors (TKI)
Imatinib
Mastinib
Toceranib
Which tyrosine kinase inhibitors (TKI) are licensed in veterinary medicine?
Mastinib and toceranib are licesnced for gross mast cell tumour treatment in dogs
These are the ONLY licensced chemotherapy drugs, the rest are given under the cascade
What are the potential side effects of tyrosine kinase inhibitors?
Gastrointestinal signs
Neutropenia
Neuropathy
Liver damage
Protein-losing nephropathy
What should you monitor during treatment with tyrosine kinase inhibitors (TKIs)?
Haematology
Biochemistry
Urinalysis
This is very important to monitor for protein-losing nephropathy
How are chemotherapy drugs dosed?
Chemotherapy drugs are dosed based on body surface area
What should you be aware of when dosing chemotherapy drugs for smaller patients (below 10kg)?
When dosing chemotherapy drugs for smaller patients (less than 10kg), be aware that dosing by based on body surface area won’t be as accurate so you may have to underdose or dose based on mg/kg to be safe
How do you calculate chemotherapy drug doses?
- Convert the patient’s body weight in kg to m^2
- Multiply the patient’s body surface area by the drug dose in mg/m^2 to get the mg of drug required
- Convert mg to ml (1mg = 1ml)
How can you convert a patient’s body weight in Kg into m^2?
Either use the formula or a conversion chart if it is available
(T/F) You can split chemotherapy tablets
FALSE. You should never split chemotherapy tablets
What can you do if the dose of the chemotherapy tablet is too high for the patient?
Increase the dosing interval
Have the drugs reformulated to match your exact dose
What are the main risks of cytotoxic drugs for handling personnel?
Cytotoxic drugs can be carcinogenic, mutagenic and tetratogenic as well as have more local irritant and vesicant (blistering) effect
Which individuals should never handle cytotoxic drugs?
Persons under 18 years old
Pregnant or breastfeeding women
Immunocomprimised individuals
What are the risks of exposure to cytotoxic drugs?
Absorption via the skin
Absorption via mucous membranes
Aerosol formation when drawing up/administering drugs
Self-inoculation when adminstering injectable drugs
Handling of cytotoxic waste
Patient excreta
Patient secretions
How can we minimise exposure to cytotoxic drugs?
Do not eat, drink, store food or smoke in areas where cytotoxic drugs are stored, prepared or administered
Wear PPE
Use best practice when handling cytotoxic drugs and waste
Use hazard signs
Which PPE should you wear when handling cytotoxic drugs and waste?
Double gloved
Gown
Eye shield
Face mask with an FFP3 filter
What is the gold standard method to avoid aerolisation of chemotherapy drugs?
Laminar flow biological safety cabinet
However this generally won’t be seen in general practice
Which methods are typically used to avoid aerolisation of chemotherapy drugs in general practice?
Careful drug preparation in a quiet, well ventilated room over a tray with an absorbant liner to contain spillages. Use luer-lock syringes or closed systems if available
What are the benefits of closed systems for preparation of cytotoxic drugs?
Prevent aerolisation
Prevent spillage
What are the disadvantages of closed systems for preparation of cytotoxic drugs?
Increased cost
May not get all of the drug out of the vial
How can you prepare cytotoxic drugs without a closed system?
- Use a quiet, well ventilated room with a tray and an absorbent liner
- Spike the drug vial with a needle whilst the vial is upright
- Invert the bottle, wrap a swab around the vial and withdraw the drug
- Re-invert the vial to an upright position
- Wrap the swab around whilst withdrawing the needle to collect any aerosols
What can be done to minimise the risk of exposure when administering cytotoxic drugs?
Good patient restraints (may require sedation)
Administrator and handler should wear PPE
Use a closed administration system
Use intravenous catheters
What are the benefits of using intravenous catheters when administering cytotoxic drugs?
Prevents perivascular reactions
Allows for thorough saline flushing
Can keep the system closed when using a T-connector
What is the ‘first stick’ rule?
It is important not to administer cytotoxic drugs via an intravenous catheter if it wasn’t placed on the first attempt as there is an increased of extravasation of the drug and perivascular reactions
What should you do if there is cytotoxic drug extravasation?
- Stop the injection
- Suck back as much of the drug as possible
- Cold compress, except for vinca alkaloids where you should use a warm compress
- Discuss this complication with the owners
- Wound management for perivascular reactions, may require surgical debridement and skin grafts
What are the benefits of using closed adminsitration systems for cytotoxic drugs?
Closed (needle-less) systems facilitate safe administration and minimise the release of droplets into the environment, thus reducing staff exposure
How do you administer an IV bolus of cytotoxic drug without a closed administration system?
- Check the patency of the IV catheter by first flushing with saline
- Carefully insert the needle into the injection port
- Cover with a swab and inject the cytotoxic drug
- Wrap the swab around the needle when removing it to collect any droplets
- Flush the IV catheter with copious amounts of saline before remove the catheter
How do you administer subcutaneous or intramuscular injections of cytotoxic drugs without a closed administration system?
- Use a luer lock syringe to attach to the needle
- After inserting the needle into the patient, place an alcohol soaked swab over the site before injecting the cytotoxic drug
- Keep the swab over the area when removing the needle
What are the rules for administering oral cytotoxic drugs?
Always wear gloves
Never split the tablets
Never crush the tablets
Always give the tablets whole
How do you administer oral cytotoxic drugs?
Whilst wearing gloves, administer the tablets with a small amount of food to allow for easier administration, and ensure the patient has swallowed to drug by squirting water into their mouth with a syringe
What is important to include when dispensing oral cytotoxic drugs to clients?
It can be helpful to place ‘warning tape’ on the cytotoxic drug container as well as send the clients home with plenty of gloves
What are the two possible routes of administration for cytotoxic drugs in horses?
Intravenous administration
Intralesional administration
Intralesional beads (beads containing chemotherapy drugs implanted into the lesion)
What is the procedure if there is a cytotoxic drug spillage?
- A cytotoxic spill kit should be available in case of accidental spills
- Alert members of staff
- Wear PPE if not doing so already
- Contain the spill using the spill kit
- Put any contaminated items into polythene bags
- Wash surfaces with copius water but make sure to wear a full respiratory mask in case of aerosols
Where should cytotoxic waste be disposed of?
Cytotoxic waste should be disposed in cytotoxic waste bins. The contents of these will be incinerated
Which organ metabolises chemotherapy drugs?
Liver
Where are chemotherapy drugs excreted?
Urine
Faeces
Saliva
How long should you barrier against patients undergoing chemotherapy to prevent exposure to cytotoxic drugs?
Recent research suggests that the excretion time is approximately 7 days so you should barrier against these patients for up to 7 days post chemotherapy administration to prevent exposure to cytotoxic drugs
Which aftercare precautions should be taken within the clinic to prevent exposure to cytotoxic drugs?
- Have properly trained staff
- Wear PPE when handling the patient
- Warning sign on the kennel door
- All excreta and kennel liners need to be disposed of as cytotoxic waste
- Use alginate laundry bags for patient bedding
- Beware of aerosols when cleaning the kennel
- Place a warning on laboratory samples explaining this patient is on chemotherapy and there is a risk of exposure
Which aftercare precautions should be taken at home to prevent exposure of clients to cytotoxic drugs?
- Provide clients with an information sheet and discuss through it at discharge
- Minimise contact between the pet and young children, pregnant women, immunosuppressed individuals
- Discourage pets from sleeping in the owners beds and wash pet bedding regularly
- Good hygiene
- Wear gloves when cleaning any excreta
- Bag and bin any faeces
- Carry around a water bottle to dilite any urination on walks etc.
- Walk dogs in quiet or remote areas (away from childrens parks etc.)
- Discourage cats from walking on food preparation areas and disinfect surfaces before use
- Use a plastic litter tray with liners
- Clean the litter tray as soon as you can
