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Module 17 > Cancer Treatment: Chemotherapy > Flashcards

Cancer Treatment: Chemotherapy Flashcards

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
Q

what is the maintenance phase of COP

A

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

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26
Q

what drug does hemorrhagic cystitis occur with

A

cyclophosphamide

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27
Q

how does cyclophosphamide cause hemorrhagic cystitis

A

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

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28
Q

how is hemorrhagic cystitis prevented

A

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)

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29
Q

how is hemorrhagic cystitis treated (3)

A
  1. stop cyclophosphamide
  2. culture urine +/- give antibiotics for secondary infection
  3. substitute chlorambucil/melphalan for cyclophosphamide in protocol
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30
Q

how do you monitor during the low dose COP

A

moderate frequency of monitoring because generally low risk of side effects (possible GI effects from vincristine)

  1. hematology (for neutropenia)
  2. urine (for hemorrhage)
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31
Q

how often should you monitor hematology in low dose COP protocols

A

baseline before treatment

monthly if all normal at start or more frequently if concerned about neutropenia

check if unexplained pyrexia, illness at any time

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32
Q

how often should you monitor urine in low doses COP

A

weekly dipstick

monthly urinalysis

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33
Q

what is the COP high dose

A

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

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34
Q

what is the induction phase of high dose COP

A

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

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35
Q

what is the maintenance phase of high dose COP

A

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
Q

what is the CHOP protocol

A

Cyclophosphamide

Hydroxydaunorubicin = doxorubicin (adriamycin)

vincristine (oncovin)

Prednisolone

37
Q

what is the induction phase of CHOP protocol

A

induction phase over 10 weeks is essentially 2 cycles of 4 drugs, given as weekly pulses

38
Q

what should you do if the animal is in complete remission after 2 cycles in the CHOP protocol

A

go to maintenance phase

39
Q

what is the maintenance phase of CHOP

A
  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
Q

what drug does cardiotoxicity occur with in the CHOP protocol

A

doxorubicin

41
Q

what is the acute effects with singe use of doxorubicin

A

acute arrhythmias

variable ECG findings

42
Q

what is the chronic cumulative effect of doxorubicin

A

myocytolysis, myofibre swelling, degeneration, vacuolation, late fibrosis

dilated cardiomyopathy

congestive heart failure

increased risk in breeds with cardiomyopathy

43
Q

how do you prevent cardiotoxicity (5)

A
  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
Q

what does hypersensitivity reaction look like

A

vomiting

restlessness

pruritis

wheals

edema

dyspnea

mouth breathing (Cat)

45
Q

how do you prevent hypersensitivity reactions

A

use antihistamine premedication

ensure correct route of admin

administer slowly for doxorubicin

46
Q

how do you treat hypersensitivity

A

stop drug admin

IV fluids

antihistamines

dexamethasone

adrenaline

47
Q

how is CHOP protocol monitored

A

high risk of side effects therefore freq monitoring is essential to use the drugs safely

48
Q

what should you monitor CHOP procotol (3)

A
  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
Q

how is neutropenia managed in CHOP

A
50
Q

what are the GI effects seen in CHOP protocols (4)

A
  1. anorexia
  2. vomiting
  3. diarrhea
  4. colitis
51
Q

how are the GI effects managed (4)

A
  1. anti-emetics
  2. gut protectants/antacids
  3. anti-diarrheal agents
  4. fluids
  5. stop tablets/chemotherapy temporarily until animal has recovered
52
Q

what acute tumour lysis syndrome and what does it cause

A

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
Q

what are the signs of acute tumour lysis syndrome

A

acute depression, bradycardia, vomiting, diarrhea, shock

54
Q

how is acute tumour lysis syndrome treated

A

treat with fluids and supportive care

55
Q

how is alopecia managed

A

generally not a problem

coat thinning, whisker loss

slow to regrow after clipping

56
Q

what is multidrug resistance encoded by

A

MDR1 gene

ATP binding cassette transporter pumps out drugs from cell

induces cross resistance to other drugs

57
Q

what are the affected drugs of multidrug resistance

A

vinca alkaloids

anthracylcines (dox, mitox)

actinomycin D

58
Q

what are the unaffected drugs of multidrug resistance

A

alkylating agents (melphalan, lomustine)

carboplatin

59
Q

what occurs if there is relapse therapy for lymphoma

A

start induction phase again

use a novel drug (single agent)

use novel potent drug combinations

60
Q

what novel drugs could you use in relapse therapy for lymphoma

A

L-asparaginase

doxorubicin

lomustine

rabacfosadine (B cell)

61
Q

what novel potent drug combinations can be used in CHOP protocols if there is relapse in lymphoma (3)

A
  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
Q

what is the outcome for lymphoma with no treatment

A

1-2 months

63
Q

what is the outcome for lymphoma with steroids only

A

2-3 months

64
Q

what is the outcome for lymphoma with COP protocol

A

6-9 months

65
Q

what is the outcome for lymphoma with CHOP protocol

A

10-12 months

66
Q

how is acute lymphoblastic leukaemia ALL treated and what is the prognosis

A

similar to high grade LSA

lymphoma protocols if sufficient neutrophils

poor prognosis

67
Q

how is chronic lymphocytic leukaemia treated

A

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
Q

how is acute myeloid leukaemia treated (AML)

A

poorly established protocols

poor outcome

cytosine

doxorubicin

prednisolone

6-thioguanine

69
Q

how is chronic granulocytic leukaemia (CLG/CML) treated

A

very rare and difficult to distinguish from inflammation/infection

hydroxyurea

busulphan

70
Q

how is multiple myeloma treated with chemo

A

melphalan 2mg/m^2 daily then q48h

prednisolone 40mg/m^2 daily for 7d then 20mg/m^2 q48h

71
Q

what do you need to do before treating multiple myeloma

A

stabilize patient and make sure to address paraneoplastic complications

hypercalcemia (IV fluids)

hyperviscosity (plasmaphoresis)

secondary infection (antibiotics)

72
Q

what is the prognosis of multiple myeloma

A

can be good if no hyperviscosity

73
Q

how are solid tumours treated with chemotherapy

A

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
Q

what does the tumour growth curve look like

A
75
Q

describe how chemotherapy of solid tumours is administerd to stop growth

A
76
Q

how are hemangiosarcomas treated

A

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
Q

what is the median survival time of hemangiosarcomas

A

Varies according to site but generally short —> extended with chemotherapy (doxorubicin)

Surgery alone = 1-3 months

+ chemotherapy = 5-7 moths

78
Q

what chemo is used to treat hemangiosarcomas

A

VAC protocol:

Vincristine, Adriamycin, Cylcophosphamide

Metronomic cyclophosphamide + NSAID therapy

79
Q

how is hemangiosarcoma treated using metronomic chemotherapy

A

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
Q

what are the benefits of metronomic chemotherapy

A

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
Q

what drugs are metronomic chemotherapies usually combined with

A

anti angiogenic drugs

ex. COX inhibitors –> NSAIDs piroxicam, celecoxib

82
Q

what are metronomic chemotherapy drugs

A

cyclophosphamide

chlorambucil

lomustine

temozolamide

83
Q

how are osteosarcomas treated

A

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
Q

what are the median survival times of bone tumours

A

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
Q

what are examples of tyrosine kinase inhibitors TKIs

A

Imatinib (Gleevec)

Masitinib (masivet)

Toceranib (palladia)

86
Q

what TKIs are licensed for unresectable gross mast cell tumours in dogs

A

Masitinib (masivet)

Toceranib (palladia)

87
Q

what are side effects of TKIs

A

GI signs

PLN

Weight loss

Neutropenia

Liver damage

Monitor hematology/biochemistry and urine (protein loss)

Module 17 (31 decks)

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