Cancer Treatment (Chemotherapy) Flashcards
Chemotherapy - aims
To prolong survival
To maintain good quality life
To minimise side-effects
Rank Haemopoietic, Mast cell tumours and Sarcomas based on chemosensitivity
Drugs work best on rapidly dividing cells:
Haemo
Mast cell tumour
Sarcomas
Two types of chemotherapy treatments
Conventional (Max tolerated dose MTD)
Targeted therapies
Outline conventional chemotherapy treatment
Works on rapidly dividing cells in a non-specific way
Does not differentiate between tumour and normal cells
Minimises side-effects by allowing normal cells to recover between doses
Why should I use a combination of chemotherapy drugs to treat lymphoma
different drugs should have a different mode of action
affect different phases of the cell cycle
and have different methods of resistance
What do I need to ensure when giving a combination of chemo drugs to patient with lymphoma
Drug toxicities do not overlap
Drugs do not interfere with each other
Why should I use an established protocol in chemotherapy
Ensure each drug is effective against tumour
Avoid overlapping toxicities/ drug interactions
Ensure adequate time for cells to recover
Are side effects from chemotherapy common in animals?
Usually minimal because protocols adapted to animals
Occasionally can be severe
Need good knowledge of hazards and careful monitoring to prevent side-effects!
Need to educate clients as to what to look out for!
Most common side effects of chemotherapy
Bone marrow suppression,
Alopecia,
GI upsets,
Outline chemotherapy for lymphoma
Treat any concurrent disease first
Eg Antibiotics for skin infection,iv saline diuresis for hypercalcaemia
Use specific chemotherapy
Induce clinical remission with high doses
Continue with maintenance (lower doses)
Intensify protocol if response not complete or change protocol to different drugs
Monitor for side-effects
What could I do if there is no evidence chemotherapy is working for patient
add a boost eg L-asparaginase or change protocol
What should I do if animal is showing sign of side effects after last dose
consider dose reduction, more GI protectants /anti-nausea drugs
OR change drugs /protocol
OR stop treatment
What are the drugs in COP protocol
Cyclophosphamide
Vincristine (Oncovin)
Prednisolone
Outline the induction phase in the COP protocol
Continuous every other day tablet administration /weekly injections
High doses of drugs for 1st 6-8 weeks to induce remission
Outline maintenance phase after induction in low dose COP protocol
Alternate week therapy (week of drugs, week of no drugs, week of drugs etc)
then 1 week in 3, 1 week in 4 etc for up to 2 years if the animal survives that long
Change cyclophosphamide to chlorambucil after 6 months to reduce risk of haemorrhagic cystitis developing.
What could cyclophosphamide cause in the long term
Haemorrhagic cystitis
Prevention of haemorrhagic cystitis
Give cyclophosphamide tablets in a.m.
Encourage drinking and urination (Prednisolone is helpful!)
Monitor urine for traces of BLOOD by dipstick (cheap) or urinalysis (precise)
Administer a diuretic (furosemide) at time of administration if infrequent use of cyclophosphamide eg CHOP
Treatment for haemorrhagic cystitis
Stop cyclophosphamide
Culture urine ± give antibiotics for secondary infection
Substitute chlorambucil /melphalan for cyclophosphamide in protocol.
When is high dose COP protocol suitable
Useful for cats where 50mg tablet size can be difficult to dose accurately or for animals/owners that want fewer visits
What is the CHOP protocol
Cyclophosphamide
Hydroxydaunorubicin = doxorubicin (Adriamycin)
Vincristine (Oncovin)
Prednisolone
Induction phase over 10 weeks is essentially 2 cycles of 4 drugs, given as weekly pulses
What chemo drug is cardiotoxic
Hydroxydaunorubicin = doxorubicin (Adriamycin)
Prevention of cardiotoxicity in chemotherapy
Assess cardiac function prior to 1st dose and continue to monitor after 4-6 doses
Baseline echocardiography measurements of
- Fractional shortening (Contractility)
- Ejection fraction
Do not exceed cumulative dose 180mg/m2
Consider less cardiotoxic equivalent drugs
What chemo drug could cause hypersensitivity
Occurs occasionally with Doxorubicin, L-asparaginase
What side effects are caused by hypersensitivity
Vomiting, restlessness, pruritus, wheals, oedema
Dyspnoea, mouth breathing (cat)
Prevention of side effects caused by hypersensitivity
Use Antihistamine premedication
Ensure correct route of administration (sc or im for L-asp)
Administer very slowly for doxorubicin
Treatment for hypersensivity
STOP drug admin
IV fluids
Antihistamines
Dexamethasone
Adrenaline
Avoid using the drug again
Things to monitor when using CHOP protocol
Haematology (neutropenia)
- Baseline before treatment
- Weekly
Urine (haemorrhagic cystitis)
- Baseline
- After each cyclophosphamide admin/prior to next
Echocardiography (heart contractility)
- Baseline
- At 4th Doxorubicin treatment
Level of neutrophils to stop/reduce giving chemo
Lower than 2.5
What is Acute tumour lysis syndrome
Large tumour burden - rapid cell kill in 1st week
Rapid release of ions, i-cellular products
HyperK+, hyper PO4-, hypoCa2+
Metabolic acidosis, uric acid production
Acute renal failure
Improves after 1st week
Name of protein causing chemodrug resistance
Multidrug resistance protein 1 (MDR1) –also called P-glycoprotein (p170) encoded by (MDR1) gene
Drugs affected by P-glycoprotein (p170)
Vinca alkaloids
Anthracyclines (Dox, Mitox),
Actinomycin D
Drugs not affected by P-glycoprotein (p170)
Alkylating agents (melphalan, lomustine)
Carboplatin
Relapse therapy for Lymphoma
Start induction phase again – go back to beginning
Use novel drug (single agents)
Use novel potent drug combinations
Mean survival after diagnosis of lymphoma with no treatment
1-2 months
Mean survival after diagnosis of lymphoma with steroids
2-3 months
Mean survival after diagnosis of lymphoma with COP protocol
6-9 months
Mean survival after diagnosis of lymphoma with CHOP protocol
10-12 months
Acute lymphoblastic (ALL) chemotherapy treatment
Similar to high grade LSA
Lymphoma protocols if sufficient neutrophils
Prognosis poor
Chronic lymphocytic (CLL) chemotherapy treatment
Similar to low grade LSA (mature lymphocytes, slowly dividing)
No treatment needed in some cases (mild)
OR Chlorambucil, Prednisolone
Solid tumours are sensitive to chemotherapy (T/F)
False!
Treatment for solid tumours
Use surgery (or radiotherapy) to remove the tissue bulk and stimulate division of any residual tumour cells
Use adjuvant chemotherapy for residual primary tumour (microscopic)
Use adjuvant chemotherapy to delay growth of subclinical metastases
Haemangiosarcoma
highly malignant cancer arising from cells that normally create blood vessels. It most commonly affects the spleen, liver, right atrium of the heart, and skin
Treatment for haemangiosarcoma
Chemotherapy with single agent Doxorubicin q3 weeks for 4-6 doses to delay metastasis
Survival time for haemangiosarcoma with just surgery
1-3 months
Survival time for haemangiosarcoma with surgery and chemo
5-7 months
What protocol for haemangiosarcoma?
VAC protocol used by some centres (Vincristine, Adriamycin, Cyclophosphamide)
Metronomic cyclophosphamide +NSAID therapy also tried (antiangiogenic and immunomodulatory)
What is Metronomic chemotherapy (MC)
Cytotoxic drugs given at LOW doses on a more continuous DAILY administration protocol rather than as high doses in pulses
Advantages of metronomic chemotherapy
Prevents repair and repopulation of endothelial cells in breaks needed with MTD therapy – anti-angiogenic
May also reduce Tregs –immunomodulatory
May target dormant cells and cancer stem cells - prevents tumour repopulation
Low doses mean fewer side-effects – well tolerated
Usually combined with other anti-angiogenic drugs eg COX inhibitors - NSAIDs – piroxicam, celecoxib
Osteosarcomas often metastasis to which organ?
Lungs
Treatment for osteosarcomas
Amputation for primary tumour (possibly limb salvage or radiotherapy for pain relief)
Chemotherapy with single agent Carboplatin for 4-6 doses to delay metastasis
Median survival time of bone tumor with no treatment
1 month
Median survival time of bone tumor with amputation alone
3-4 months
Prognosis of osteosarcomas
Rapid euthanasia if no pain relief possible.
Rapid metastatic spread if no chemotherapy.
Median survival time of bone tumor with amputation and chemo
> 10 months
Summarise Tyrosine kinase inhibitors (TKIs)
Tyrosine kinase inhibitors (TKIs) are a class of medications used in cancer treatment that work by targeting specific enzymes called tyrosine kinases. These enzymes are often overactive in cancer cells, leading to uncontrolled cell growth and proliferation. By inhibiting these enzymes, TKIs help to slow down or stop the growth of cancer cells.
