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Module 17 > Cancer Treatment: Chemotherapy > Flashcards

Cancer Treatment: Chemotherapy Flashcards

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1
Q

how is chemo in vet med different to human med

A

much lower doses and fewer side effects

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2
Q

what are the aims of chemotherapy

A

To prolong survival

To maintain good quality life

To minimize side effects

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3
Q

how is a patient selected for chemotherapy (4)

A

1. Confirm the diagnosis of neoplasia and stage the clinical extent

-Blood +/- marrow to assess marrow function in hemopoietic tumours

2. Treat/stabilize paraneoplastic syndromes

3. Decide that systemic treatment is appropriate and necessary (wide spread or highly metastatic tumour)

4. Exclude concurrent disease which may prevent chemotherapy (stop NSAIDs for arthritis is planning to use prednisolone)

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4
Q

which tumorus is chemotherapy most effective on

A

drugs work best on rapidly dividing cells

Hematopoietic (LSA/leukaemia)

Mast cell tumours (high grade)

Solid carcinomas/sarcomas

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5
Q

what is conventional chemotherapy

A

non-specific toxic effect of high doses of cytotoxic drugs acting on any dividing cells

max tolerated dose

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6
Q

what are targeted therapies

A

Drugs which specifically target pathways or molecules only altered in cancer cells

Should have reduced side-effects if only cancer cells affected

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7
Q

how does conventional chemotherapy work

A

Works on rapidly dividing cells in a non-specific way

Doesn’t differentiate between tumour and normal cells

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8
Q

how do you minimize side effects when using conventional chemotherapy

A

allow normal cells to recover between doses

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9
Q

how do chemotherapy drugs work on the cell cycle

A
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10
Q

why should you use a combination of drugs when treating lymphoma (3)

A
  1. different drugs should have a different mode of action
  2. affect different phases of the cell cycle
  3. and have different methods of resistance
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11
Q

what do you need to make sure of when combining drugs

A
  1. drug toxicities don’t overlap
  2. drugs do not interfere with eachother
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12
Q

what are the general side effects of chemotherapy drugs

A

bone marrow suppression

alopecia

GI upsets

delayed effects (infertility, new tumour induction)

perivascular reaction/irritation

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13
Q

what are side effects of cyclophosphamide

A

hemorrhagic cystitis

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14
Q

what are side effects of doxorubicin

A

cardiomyopathy

arrhythmias

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15
Q

what are side effects of lomustine

A

liver damage

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16
Q

what are side effects of vincristine, vinblastine

A

peripheral neuropathies

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17
Q

what are side effects of cisplatin

A

nephrotoxicity

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18
Q

which drugs can cause hypersensitivity

A

doxorubicin

L-asparaginase

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19
Q

how do you chose a protocol to treat lymphoma (5)

A
  1. B cell/T cell
  2. high grade/low grade
  3. induce clinical remission with high doses
  4. continue with maintenance (lower doses)
  5. intensify protocol if response not complete or change to different drugs
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20
Q

how do you assess if chemotherpy is effective

A

1. is animal in remission (is there evidence drugs are working)

yes = continue

no = add a boost (ex. L-asparaginase or change protocol)

2. is animal well with no unacceptable side effects after last dose?

yes = continue

no = consider dose reduction, more GI protectants/anti nausea or change drugs/protocols or stop treatment

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21
Q

what is low dose COP protocol

A

vincristine (Oncovin)

Cyclophosphamide

Prednisolone

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22
Q

what is the induction phase of low dose COP

A

high doses of drugs for first 6-8 weeks to induce remission

vincristine: 0.5mg/m^2 IV q7 days

cyclophosphamide 50mg/m^2 po q48h

prednisolone 40mg/m^2 po 24h for 7 days, then 20mg/m^2 po q48h

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23
Q

if the animal is in clinical remission with the low dose COP protocol what should you do

A

go to maintenance doses

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24
Q

if the animal is in partial remission or stable disease (SD) with the low dose COP protocol what should you do

A

keep on weekly or change protocol

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25
what is the maintenance phase of COP
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 hemorrhagic cystitis developing
26
what drug does hemorrhagic cystitis occur with
cyclophosphamide
27
how does cyclophosphamide cause hemorrhagic cystitis
due to metabolite acrolein in contact with bladder wall usually sterile cystitis --\> hematuria, dysuria but may get secondary bacterial component so culture to be sure
28
how is hemorrhagic cystitis prevented
give cyclophosphamide in morning 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 (CHOP) use a uroprotectant concurrently -- MESNA (IV or oral)
29
how is hemorrhagic cystitis treated (3)
1. stop cyclophosphamide 2. culture urine +/- give antibiotics for secondary infection 3. substitute chlorambucil/melphalan for cyclophosphamide in protocol
30
how do you monitor during the low dose COP
moderate frequency of monitoring because generally low risk of side effects (possible GI effects from vincristine) 1. hematology (for neutropenia) 2. urine (for hemorrhage)
31
how often should you monitor hematology in low dose COP protocols
baseline before treatment monthly if all normal at start or more frequently if concerned about neutropenia check if unexplained pyrexia, illness at any time
32
how often should you monitor urine in low doses COP
weekly dipstick monthly urinalysis
33
what is the COP high dose
3 weekly pulses of drugs rather than daily/EOD tablets useful for cats where 50mg tablet size can be difficult to dose accurately or for animals/owners that want fewer visits
34
what is the induction phase of high dose COP
vincristine (oncovin) 0.75mg/m^2 IV q7 days for 28 days, then q21 days cyclophosphamide 250 mg/m^2 IV (po) q21 days prednisolone 1mg/kg po q24h for 28 days, then q48h
35
what is the maintenance phase of high dose COP
after ~6 months, reduce cycle to every 4 weeks after ~12 months, reduce cycle to every 5 weeks after ~18 months, reduce cycle to every 6 weeks substitute chlorambucil or melphalan if hemorrhagic cystitis develops
36
what is the CHOP protocol
**C**yclophosphamide **H**ydroxydaunorubicin = doxorubicin (adriamycin) vincristine (**o**ncovin) **P**rednisolone
37
what is the induction phase of CHOP protocol
induction phase over 10 weeks is essentially 2 cycles of 4 drugs, given as weekly pulses
38
what should you do if the animal is in complete remission after 2 cycles in the CHOP protocol
go to maintenance phase
39
what is the maintenance phase of CHOP
1. repeate 10 week cycle with 2 weeks between drug administration 2. total of 25 weeks (6 months) although some 12 week modified protocols available can substitute chlorambucil for cyclophosphamide if hemorrhagic cystitis occurs
40
what drug does cardiotoxicity occur with in the CHOP protocol
doxorubicin
41
what is the acute effects with singe use of doxorubicin
acute arrhythmias variable ECG findings
42
what is the chronic cumulative effect of doxorubicin
myocytolysis, myofibre swelling, degeneration, vacuolation, late fibrosis dilated cardiomyopathy congestive heart failure increased risk in breeds with cardiomyopathy
43
how do you prevent cardiotoxicity (5)
1. assess cardiac function prior to 1st dose and continue to monitor after 4-6 doses 2. baseline echocardiography measurements of fractional shortening, ejection fraction 3. measure serum ctroponin I 4. do not exceed cumulative dose 180mg/m^2 5. consider less cardiotoxic equivalent drugs: epirubicin, mitoxantrone
44
what does hypersensitivity reaction look like
vomiting restlessness pruritis wheals edema dyspnea mouth breathing (Cat)
45
how do you prevent hypersensitivity reactions
use antihistamine premedication ensure correct route of admin administer slowly for doxorubicin
46
how do you treat hypersensitivity
stop drug admin IV fluids antihistamines dexamethasone adrenaline
47
how is CHOP protocol monitored
high risk of side effects therefore freq monitoring is essential to use the drugs safely
48
what should you monitor CHOP procotol (3)
1. hematology (neutropenia): baseline before treatment, weekly 2. urine (hemorrhagic cystitis): baseline, after each cyclophosphamide admin/prior to next 3. echocardiography (heart contractility): baseline, at 4th doxorubicin treatment
49
how is neutropenia managed in CHOP
50
what are the GI effects seen in CHOP protocols (4)
1. anorexia 2. vomiting 3. diarrhea 4. colitis
51
how are the GI effects managed (4)
1. anti-emetics 2. gut protectants/antacids 3. anti-diarrheal agents 4. fluids 5. stop tablets/chemotherapy temporarily until animal has recovered
52
what acute tumour lysis syndrome and what does it cause
**large tumour burden rapid cell kill in 1st week** -rapid release of ions, i-cellular products hyperkalemia, hyperphosphatemia, hypocalcemia metabolic acidosis, uric acid production acute renal failure
53
what are the signs of acute tumour lysis syndrome
acute depression, bradycardia, vomiting, diarrhea, shock
54
how is acute tumour lysis syndrome treated
treat with fluids and supportive care
55
how is alopecia managed
generally not a problem coat thinning, whisker loss slow to regrow after clipping
56
what is multidrug resistance encoded by
MDR1 gene ATP binding cassette transporter pumps out drugs from cell induces cross resistance to other drugs
57
what are the affected drugs of multidrug resistance
vinca alkaloids anthracylcines (dox, mitox) actinomycin D
58
what are the unaffected drugs of multidrug resistance
alkylating agents (melphalan, lomustine) carboplatin
59
what occurs if there is relapse therapy for lymphoma
start induction phase again use a novel drug (single agent) use novel potent drug combinations
60
what novel drugs could you use in relapse therapy for lymphoma
L-asparaginase doxorubicin lomustine rabacfosadine (B cell)
61
what novel potent drug combinations can be used in CHOP protocols if there is relapse in lymphoma (3)
1. DMAC: dexamethasone, melphalan, actinomycin D, cytosine arabinoside 2. ALP: L-asparaginase, lomustine, prednisolone 3. MOPP or LOPP: mechlorethamine or lomustine, vincristine, procarbazine, prednisolone
62
what is the outcome for lymphoma with no treatment
1-2 months
63
what is the outcome for lymphoma with steroids only
2-3 months
64
what is the outcome for lymphoma with COP protocol
6-9 months
65
what is the outcome for lymphoma with CHOP protocol
10-12 months
66
how is acute lymphoblastic leukaemia ALL treated and what is the prognosis
similar to high grade LSA lymphoma protocols if sufficient neutrophils poor prognosis
67
how is chronic lymphocytic leukaemia treated
similar to low grade LSA (mature lymphocytes, slowly dividing) no treatment needed in some cases OR chlorambucil 2-4mg/m^2 daily, then q48h prednisolone 40mg/m^2 daily then 20mg/m^2 q48h
68
how is acute myeloid leukaemia treated (AML)
poorly established protocols poor outcome cytosine doxorubicin prednisolone 6-thioguanine
69
how is chronic granulocytic leukaemia (CLG/CML) treated
very rare and difficult to distinguish from inflammation/infection hydroxyurea busulphan
70
how is multiple myeloma treated with chemo
melphalan 2mg/m^2 daily then q48h prednisolone 40mg/m^2 daily for 7d then 20mg/m^2 q48h
71
what do you need to do before treating multiple myeloma
stabilize patient and make sure to address paraneoplastic complications hypercalcemia (IV fluids) hyperviscosity (plasmaphoresis) secondary infection (antibiotics)
72
what is the prognosis of multiple myeloma
can be good if no hyperviscosity
73
how are solid tumours treated with chemotherapy
not usually chemosensitive use surgery (or radiotherapy) to remove the tissue bulk and stimulate division of any residual tumour cells use adjuvant chemo for residual primary tumour (microscopic) use adjuvant chemo to delay growth of subclinical metastasis
74
what does the tumour growth curve look like
75
describe how chemotherapy of solid tumours is administerd to stop growth
76
how are hemangiosarcomas treated
Splenic mass with rapid metastasis to lungs (and organs of abdominal cavity) Chemotherapy with single agent doxorubicin q3 weeks for 4-6 doses to delay metastasis
77
what is the median survival time of hemangiosarcomas
Varies according to site but generally short —\> extended with chemotherapy (doxorubicin) Surgery alone = 1-3 months + chemotherapy = 5-7 moths
78
what chemo is used to treat hemangiosarcomas
**VAC protocol:** Vincristine, Adriamycin, Cylcophosphamide **Metronomic cyclophosphamide + NSAID therapy**
79
how is hemangiosarcoma treated using metronomic chemotherapy
Antiangiogenic and immunomodulatory Cytotoxic drugs given at LOW doses on a more continuous DAILY administration protocol rather than as high doses in pulses Prevents repair and repopulation of endothelial cells in breaks needed with MTD therapy —\> anti-angiogenic (prevents blood vessels that supply the tumour from regrowing)
80
what are the benefits of metronomic chemotherapy
May also reduce T regs —\> **immunomodulatory** May target dormant cells and cancer stem cells —\> **prevents tumour repopulation** low doses mean fewer side effects (well tolerated)
81
what drugs are metronomic chemotherapies usually combined with
anti angiogenic drugs ex. COX inhibitors --\> NSAIDs piroxicam, celecoxib
82
what are metronomic chemotherapy drugs
cyclophosphamide chlorambucil lomustine temozolamide
83
how are osteosarcomas treated
amputation for primary tumour (possibly limb salvage or radiotherapy for pain relief) chemotherapy with single agent carboplatin for 4-6 doses to delay metastasis
84
what are the median survival times of bone tumours
No treatment = 1 month Amputation alone = 3-4 months + cisplatin = 10-13 months + carboplatin = 10 months + doxorubicin = 12 months + cisplatin + dox (alt) = 10 months + cisplatin + dox (combo) = 11-18 months
85
what are examples of tyrosine kinase inhibitors TKIs
Imatinib (Gleevec) Masitinib (masivet) Toceranib (palladia)
86
what TKIs are licensed for unresectable gross mast cell tumours in dogs
Masitinib (masivet) Toceranib (palladia)
87
what are side effects of TKIs
GI signs PLN Weight loss Neutropenia Liver damage Monitor hematology/biochemistry and urine (protein loss)

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