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oncoloy > cancer therapies > Flashcards

cancer therapies Flashcards

1
Q

what’s the rationale behind chemotherapy?

A

targets key players in cell cycle to prevent progression of the cell cycle and thus induce apoptosis therefore cytotoxic
therefore mainly affects rapidly dividing cells.

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2
Q

what are the different ways in which chemotherapy is used?

A

neoadjuvant - shrink tumour before surgery.

adjuvant - after surgery to reduce chance of prolapse by reducing any micromets

primary therapy - haematological malignancies
palliative - symptom control, prolong life and improve quality
maintainance therapy - maintain growth of cancer to a minimum can last from weeks to years depending on cancer and how well side effects are tolerated

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3
Q

what are the pros and cons of neoadjuvant chemotherapy?

A

improves surgery outcome
can see the impact of chemo - can visualise the shrinkage

however delays surgical time and thus gives opportunity for progression

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4
Q

what are the pros and cons of adjuvant chemotherapy?

A

can reduce chance of micrometastasis

however cant monitor whether it is having an effect just hope it doesn’t reoccur

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5
Q

list the different classes of chemotherapy agents. give an example of each.

A

antimetabolites - methotrexate, 5 flurouracil

alkylating agents - cyclophosphamide

platinums - cisplatin

vinca alkaloids and taxanes - vincistrine

DNA interfering agents - bleomycin

DNA topoisomerase inhibitors - doxorubicin

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6
Q

what do alkylating agents do? (chemo)

A

bind alkyl groups on DNA and cross link DNA strands

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7
Q

what do platinums do? (chemo)

A

work in a very similar way to alkylating agents and cross link DNA but in a different way. they also intercalate DNA

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8
Q

what do antimetabolities (chemotherapy) do ? use 2 examples

A

mimic normal substrates to block the production of metabolites needed for replication.

e. g. methotrexate block DHFR and thus reduces nucleotide production
e. g. 5 flurouracil - inhibits thymidylate synthesis and thus thymine cannot be produced

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9
Q

what do vinca alkaloids do?

A

mitotic inhibitors - inhibit formation of microtubules

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10
Q

what does bleomycin do?

A

DNA interfering agent - inserts itself into DNA to prevent replication

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11
Q

what does doxorubicin do?

A

topoisomerase inhibitor.
topoisomerase normally helps stabilise DNA during replication by preventing supercoiling.
therefore doxorubicin causes supercoiling and cessation of DNA replication

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12
Q

chemotherapy agents have a narrow therapeutic index what does this mean when we calculate doses for patients?

A

need to be careful and calculate dose for each individual patient depending on

  • BMI and body surface
  • their ability to metabolise the drug - kidney and renal function
  • general well being (performance status)

to avoid toxicity

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13
Q

how are chemotherapy agents delivered to the patient?

A

IV, oral or subcutaneously

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14
Q

what is the problem with delivery some chemotherapies peripherally?

A

chemotherapies are quite toxic drugs and thus can damage peripheral veins
can cause extravasation - local tissue necrosis of peripheral vein

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15
Q

what is meant by a chemo cycle? how long is a cycle?

A

chemotherapies are usually prescribed in cycles to allow bone marrow recovery between each cycle

length of cycle and no. of cycles depends on drugs

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16
Q

why do cancer cells develop resistance quickly and how can we aim to combat this?

A

rapidly dividing and genetically unstable and thus have a high mutation rate.
so can quickly develop mutations giving them resistance against chemotherapy agents

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17
Q

when using multidrug regime of chemo to combat resistance what must we ensure about the different drugs?

A

different targets
different toxicity
different mechanisms of resistance

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18
Q

what are the different resistance mechanisms cancer cells develop?

A 
efflux pumps - ejection of chemo agent 
decrease uptake of drug
increase drug metabolism 
alter drug target
increase expression or affinity of target enzyme 
impair apoptotic pathways
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19
Q

why do chemotherapies have many side effects?

A

not selective to tumour cells alone.
target any rapidly dividing cell and thus other tissue types in the body are affected - gut, bone marrow, hair follicles etc

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20
Q

list the common side effects of chemotherapy

A

hair - alopecia - reduces self esteem

brain - chemobrain (cant function the same), peripheral neuropathy, fatigue, psychological distress

lungs - pneumonitis leads to SoB and restrictive lung pattern and ILD e.g. bleomycin. also can get P.Es

heart - cardiomyopathy

stomach/ GIT - N+V, diarrhoea/ constipation and mucositis

liver - deranged LFTs
kidney - AKI, electrolyte disturbance
bladder - haemorrhagic cystisis

repro - impaired fertility, premature menopause and reduced labido

skin - rash, nail loss, palmar plantar erythema (dry hands and feet)

blood - myelosuppression

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21
Q

how can we prevent anticipatory nausea and vomiting?

A

prevent N+V on first chemo dose

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22
Q

what is the problem with mucositis ?

A

painful oesophagus and mouth
can prevent eating
predisposed to thrush

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23
Q

what are beau’s lines?

A

with chemo you get nail loss and thus with each cycle of chemo a line is shown on your nails. count the lines = no. of cycles

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24
Q

chemotherapy can cause myelosuppression what can this lead to?

A

anaemia - fatigue, SoB

thrombocytopenia - bleeding

neutropenia - infection and sepsis

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25
Q

how is nausea and vomiting from chemo managed?

A

anti emetics
ondansetron - given on day of chemo and 3 days later - prevent N+V so that anticipatory N+V doesn’t develop
metoclopramide - when needed

dexamethasone and PPI - not in diabetes

others - cyclizine and aprepitant

26
Q

how is alopecia from chemo managed?

A

cold pack on head - vasoconstriction to reduce chemo agents getting to the scalp - reduces hair loss

everyone gets a wig referral

27
Q

how is infection risk from chemo reduced?

A

prophylactic:
- antifungals - intraconazole
- co-trimoxazole - pneumocystis jivoreci
- Abx
- antivirals - aciclovir

mouth wash with chlorhexidine is recommended after every meal - mouth is main source of infection

regular blood tests to check for neutropenia

28
Q

how is mucositis from chemo treated?

A

mouth care
treat infection
can give prophylactic fluconazole for thrush

29
Q

chemotherapies are teratogens - how is this effect avoided?

A

advice to avoid pregnancy in both men and women

should use contraception but avoid COCP - thrombosis risk

30
Q

chemotherapy reduces fertility, how can we help patients with this problem?

A

council patients on this risk

offer egg freezing and sperm storage

31
Q

how can we help someone on chemo with a very low Hb count? when is this not advised?

A

can consider transfusion

however if WCC > 100 x 10^9 then contraindicated due to hyperviscosity

32
Q

where do PICC and Hickmans lines insert?

A

PICC - peripherally inserted central catheter - use peripheral vein and thread it through until it reaches a central vein

Hickmans - into SVC via chest wall.

33
Q

what is immunotherapy?

A

uses the bodys own immune system and its components to target and destroy cancer cells

involves monoclonal Ab, checkpoint inhibitors, cytokines, interferons and interleukins

34
Q

how are monoclonal Abs made?

A

inject antigen into mice and allow them to develop B cells against this antigen
hybridise this B cell with a myeloma cell such that the B cell replicates indefinitely to supply these specific Ab indefinitely

35
Q

give 4 examples of monoclonal antibody use in cancer.

A

Herceptin - HER2 receptor blocker in HER positive breast cancer

Avastin - blocks VEGF to prevent angiogenesis in breast and gastric cancers

EGFR blockers - (these can be monoclonal ab but can also get small molecule inhibitors against them) - mainly used in CRC. (EGFR is a tyrosine kinase implicated in proliferation, invasion and reduced apoptosis

rituximab - against CD20 - good for B cell lymphoma

36
Q

explain how checkpoint inhibitors work

A

our body cells express PDL1 ligand which can bind T cell and APC PD1 receptors. This allows immune cells to recognise self from non-self. tumour cells have found a way to express PDL1 such that the APC/ Tcells do not destroy them.

checkpoint inhibitors aim to block the PDL1/ PD1 interaction and thus allow tumour cells to be recognised by immune system and destroyed.
these inhibitors are monoclonal Ab

37
Q

what is imipilumumab

A

monoclonal Ab used as a checkpoint inhibitor in myeloma

38
Q

explain the side effect effects found with immunotherapy?

A

immunotherapy is effectively activating the immune system and thus can result in:

autoimmunity - thyroid, addisons, hypopituitarism, neurological autoimmune conditions, myasthenia, arthritis, vasculitis, guillian barrie, polymyalgia rheumatica etc

inflammation - hepatitis , mucositis (diarrhoea, N+V, adbo pain) , immune related dermatitis, pruritic, steven Johnson, pneumonisitis

side effects can last for months after dose

39
Q

how is autoimmunity as a result of immunotherapy treated?

A

steroid and immunosuppression

40
Q

what are targeted therapies?

A

small molecule inhibitors that target specific drivers of the cancer e.g. tyrosine kinase inhibitors
these molecules end in ib

41
Q

give an example of a targeted therapy

A

Imantinib - tyrosine kinase inhibitor in CML (BCR ABL inhibitor)

42
Q

what are the side effects of targeted therapy?

A

HTN, proteinuria, GI perforation and poor wound healing are the main 4

others - 
diarrhoea, N+V, abnormal LFTs
hair growth abnormalities , nail changes, pruritic, 
cardiac ischaemia, VTEs
flu like symptoms and allergies 
myelosuppression, fatigue
43
Q

what are the 2 ways radiotherapy works to kill tumour cells?

A

directly damages DNA with ionising radiation
produces free radicals which then damage DNA - need to ensure Hb levels are high enough in order for there to be O2 to produce free radicals

damaged DNA signals the cell to apoptose if it cannot be repaired (often tumour cells are genetically unstable)

44
Q

how are normal cells protected from radiotherapy?

A

firstly radiotherapy is directly to tumour and minimises the effect it has on surrounding normal tissue. - done by careful calculation of tumour dimension

secondly normal cells have intact repair mechanisms and thus are more likely to repair before undergoing apoptosis

45
Q

what are the different types of radiation therapy?

A

external beam (most common) - delivers radiation from an external accelerator

brachytherapy - radiation source is placed close or within tumour allowing high dose locally e.g. prostate or cervical

systemic treatments - radioactive substances injected/ swallowed and targeted to the tumour site.

46
Q

what is the difference between radical and palliative radiotherapy?

A

radical:

  • intent to cure
  • low daily dose, high total dose
  • 4-7 weeks of treatment
  • small fields of radiation

palliative:

  • reduce symptoms e.g. brain mets, bone pain, haemoptysis and dysphagia
  • 1 to 10 treatments
  • larger field of radiation
  • high daily dose - low total dose
47
Q

what are the early side effects of radiotherapy?

A

symptoms depends on site

tiredness - weeks to months

skin reactions - can vary from erythema to ulcers. use moisturiser to prevent

mucositis - avoid smoking, alcohol and spicy foods. aseptic mouthwash. treat oral thrush

N&V - caused by stomach, liver and brain radiotherapy

dysphagia and sore throat
diarrhoea - abdo and pelvic treatment. maintain hydration and give loperamide

cystitis - after pelvic treatments
bone marrow suppression
lymphaedema
hair loss

48
Q

what are the late side effects of radiotherapy involving CNS and lung?

A

years to months later

CNS

  • drowsiness after brain radiation (steroids to treat)
  • spinal cord myelopathy - progressive weakness. MRI to rule out compression
  • brachial plexopathy - after axillary radiation
  • reduced IQ in those receiving brain radiotherapy before age 6

lung - pneumonitis and fibrosis (dry cough and dyspnoea). treat with steroids

49
Q

what are radiosensitisers?

A

agents given that make tumour more sensitive to radiotherapy

conventional chemotherapy can be used in combo with radiotherapy to make radiotherapy more effective because chemo dysregulates the S phase which will reduce repair caused by radiation

e.g. cisplatin cross links DNA exacerbating the effect of radiotherapy on DNA damage

50
Q

what is radioimmunotherapy?

A

radiolabelled monoclonal Ab

delivers cytotoxic radiation to target cancer cells

51
Q

what is the role of surgery in cancer?

A

surgical biopsy for histological diagnosis - gold standard for cancer diagnosis

surgery with curative intent is main treatment for solid cancers

palliative care:

  • stents to relieve obstruction
  • insertion of Pegs
  • abdominal shunts to relieve ascites
  • debulking of large tumours that have obstructing affect e.g. SVC compression, dysphagia
52
Q

what are the different methods of biopsing cancer?

A

FNA
-can be under image guided. try avoid tumour seeding

needle core biopsy
- involved a cutting needle. try avoid tumour seeding

open surgical biopsy:
- usually whole excision rather than incision

53
Q

what are the side effects of surgery for cancer?

A

surgical complications - DVT, chest infection, surgical wound infection, bleed

anaesthetic risk

later - adhesions, strictures
nerve damage
specific problems e.g. short bowel syndrome

54
Q

how is metastatic disease normally treated?

A

initial treatment leads to a new stable state
stable state which is maintained by long term cytostatic treatment e.g. immunotherapy
eventually relapse

55
Q

is all metastatic disease incurable?

A

no, seminoma is metastatic but still can be cured quite well. however in generally usually poor prognosis

56
Q

how are neuroendocrine tumours treated?

A

somatostatin analogues
need to check if they respond to somatostatin first - octreotide scan will test for this - shows up if somatostatin receptors are present or not.

57
Q

what is the role of steroids in oncology?

A

reduce tumour size/ inflammation for cord compression

reduce N+V

increase appetite and weight gain
increase energy levels

reduce liver capsular pain when there are liver mets by reducing inflammation

58
Q

can radiotherapy be given twice?

A

not to the same place, too damaging

59
Q

what are the late side effects of radiotherapy involving skin, bone, GI, heart?

A

skin - pigmentation, ulceration, telangiectasia, necrosis

bone - necrosis, fracture, impaired growth (children)

GI - xerostomia, benign strictures, adhesions, fistulas

heart - cardiomyopathy, pericardiafibrosis

60
Q

what are the late side effects of radiotherapy involving gonads, eyes, urinary and thyroid?

A

gonads - infertility, impotence, early menopause

eyes - cataracts, reduced vision

urinary - increased frequency due to small fibrosed bladder

hypothyroid

oncoloy (13 decks)

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