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Yr4 - Cancer Care > Cancer Therapy > Flashcards

Cancer Therapy Flashcards

1
Q

Properties of cancer

A 
Self-sufficiency in growth signals
Insensitivity to anti-growth signals
Tissue invasion and metastasises
Evading apoptosis
Sustained angiogenesis
Limitless replicative potential
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2
Q

Types of cancer therapy

A

Neoadjuvant - administered before definitive treatment (surgery or radiotherapy) to shrink tumour and optimise outcomes
Adjuvant - given after treatment to reduce risk of disease recurrence
Palliative - designed to relive symptoms and improve quality of life

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3
Q

Options of cancer treatment

A 
Traditional
- chemotherapy
- radiotherapy
- surgery
Novel therapies
- immunotherapy
     - monoclonal antibodies
     - checkpoint inhibitors
- radioimmunotherapy
- drugs targeting oncogenes
- signal transduction inhibitors
- anti-apoptotic agents
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4
Q

Principles of chemotherapy

A

Treatment of cancer with drug therapy
Interfere with essential step required for cell growth and proliferation
Damaged cancer cell unable to repair damage and initiate programmed cell death - apoptosis

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5
Q

Mechanisms of cancer cell resitance

A 
Decrease uptake of drug
Increase drug metabolism
After drug targets
Impair apoptotic pathway
After cell cycle checkpoints
Efflux pumps
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6
Q

Side effects of chemotherapy

A 
Brain
- chemo-brain
- peripheral neuropathy
- fatigue
Hair
- alopecia
Heart/blood
- neutropenic sepsis
- cardiomyopathy
- myelosuppression -> bleeding from low platelets, fatigue from anaemia and sepsis
GI
- vomiting
- mucositis
- diarrhoea
- constipation
Bladder
- haemorrhagic cystitis
Skin
- PPE
- rash
- nail ridging/loss
Reproductive organs
- impaired fertility
- decreased libido
- premature menopause
Kidneys
- AKI
- electrolyte disturbances
Liver
- deranged LFTs
Lungs
- pneumonitis
- PE
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7
Q

Anti-emetics for chemotherapy

A

5HT receptor antagonists - ondansetron
- block receptors in GI tract and CNS tract
Dopamine receptor antagonist - metoclopramide
- act centrally by blocking the chemoreceptor trigger zone
Steroids - dexamethasone
Antihistamines - cyclizine
NK1 receptor antagonists - aprepitant
Antimuscarinics - hyoscine
Cannabinoids - nabilone
Benzodiazepines - midazolam, lorazepam

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8
Q

Features of tumour lysis syndrome

A

Tumour cell lysis -> hyperkalaemia
Release of DNA, phosphorus leads to Ca-Phos precipitation -> hypocalcaemia leading to arrhythmias
-> urate and Ca-Phos nephropathy
Release of purines, hypoxanthine, uric acid
- needs IV fluids, allopurinol and rasburicase

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9
Q

Features of immunotherapy

A

Uses immune system and its components to recognise, target and destroy cancer cells
Passive
- ex vivo
- activated cells or molecules that once found inside body compensate for missing or deficient immune functions
Active
- stimulates effector functions in vivo
- requires patient’s immune system to be able to respond upon challenge, stimulated and mediate effector functions

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10
Q

Types of immunotherapy

A 
Passive
- tumour-specific mAbs
- cytokines
- adoptive cell transfer
Active
- oncolytic viruses
- checkpoint inhibitors
- allogeneic whole cell vaccines
- DC vaccines
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11
Q

Features of monoclonal antibodies

A

Bind to a certain antigen on cancer cell surface, blocking specific downstream signalling pathways and arresting cell proliferation

  • HER2 inhibitors - Herceptin (Trastuzumab) in breast and gastric cancers
  • VEGR (vascular epithelial growth receptor ) inhibitors - Bevacizumab in ovarian and bowel cancer
  • EGFR inhibitor (epithelial growth factor receptor) - Cetuximab/Panitumumab in bowel cancer
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12
Q

Side effects of targeted therapies

A 
Skin toxicity
- acneform rash
- dry skin
Hair growth disorders
Pruritis
Nail changes
Fatigue
Myelosuppression
Diarrhoea
Nausea
Hypertension
Proteinuria
GI perforation
Delayed wound healing
Arterial thromboembolic events
Cardiac ischaemia
Flu-like symptoms
Abnormal LFTs
Allergic reaction
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13
Q

Features of checkpoint inhibitors

A

Can be used as single agents or in combination
CTLA4 inhibitor
- Imipilumumab - used in melanoma
PD-1/PD-LI inhibitors
- Nivolumab, Pembrolizumab used in melanoma, lung and renal cancers

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14
Q

Features of side effects of checkpoint inhibitors

A

Inflammatory adverse reactions
Increased/excessive immune activity
Can present months following last dose
Most resolve after prompt therapy or withdrawal
Corticosteroids or alternate immunosuppression led to reversal in majority

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15
Q

Side effects of checkpoint inhibitors

A 
GI
- diarrhoea
- abdo pain
- blood or mucus in stool
- bowel perforation
- peritoneal signs
- ileus
Skin
- immune-related dermatitis
- pruritus
- dry skin
- rash - Stevens-Johnson syndrome or toxic epidermal necrolysis
Hepatic
- immune related hepatitis
- symptoms of hepatotoxicity
Neuro
- immune-related neuropathies
- unilateral or bilateral weakness
- sensory alterations
- paresthesia
- myasthenia gravis
- Guillain-Barre syndrome
Endocrine
- hypophysitis
- hypopituitarism
- adrenal insufficiency
- hypothyroidism
Other
- eosinophilia
- angiopathy
- myocarditis
- temporal arteritis
- vasculitis
- blepharitis
- conjunctivitis
- episcleritis
- uveitis
- arthritis
- polymyalgia rheumatica
- nephritis
- haemolytic anaemia
- pneumonitis
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16
Q

Key points of radiotherapy

A

Use of high energy ionising radiation to treat, primarily, malignant disease
40% of all patients cured of cancer cured by radiotherapy
50% patients will benefit from receiving radiotherapy as part of cancer management
Given alone or in combination

17
Q

Action of radiotherapy

A

Direction action
- DNA damage leads to cell death
Indirect action
- free radicals, DNA damage leading to cell death

18
Q

Types of radiotherapy

A

External beam
Brachytherapy
- used as boost treatment o or primary for prostate and cervical
Systemic treatments
- radioactive substance injected or swallowed

19
Q

Radiosensitisers

A 
Make cells more sensitive to radiotherapy
Temozolamide
- oral chemo for GBM tumours
Capecitabine
- oral chemo for colorectal cancer
Cisplatin
- wide range of uses
Cetuximabe 
- monoclonal antibody
- given if prior cisplatin or cannot tolerate cisplatin
5FU
- GI tract tumours
20
Q

Features of radical radiotherapy

A

Intent to cure
Treatment duration
- 4-7 weeks
Small fields of irradiation

21
Q

Features of palliative radiotherapy

A

Alleviate symptoms
1-10 daily treatments
Larger field of irradiation

22
Q

Side effects of radiotherapy

A 
Depend on area treated
Fatigue
N+V
Erythema
Lymphoedema
Low blood counts
Dysuria
Radiation cystitis
Hair loss
Dysphagia
Sore throat
Oral mucositis
Diarrhoea
Sterility
23
Q

Types of radiotherapy

A

External beam
Brachytherapy
- prostate and cervical
IMRT - intensity modulated radiotherapy
Systemic
- radioactive substances injected/swallowed
- iodine 131 radioisotope used for thyroid cancer

24
Q

Radiosensitizers

A

Certain chemotherapies that make cells more sensitive to radiotherapy
- tamozolamide

25
Q

Define radical radiotherapy

A

Radiotherapy used to treat cancer as part of curative strategy

  • neoadjuvant
  • adjuvant
  • definitive
26
Q

Define palliative radiotherapy

A 
Symptom control - not aiming to cure
Lower dose so reduced side effects
Spinal cord compression
Pain caused by bone mets
SVCO
27
Q

Side effects of radiotherapy

A 
Depends on area treated
Fatigue
Hair loss
Dysphagia, sore throat, oral mucositis
Low blood counts
N+V
Erythema
Cystitis
Sterilisation
Radiotherapy dermatitis
28
Q

Late side effects of radiotherapy

A 
Skin
- pigmentation
- necrosis
- telangiectasia
- ulceration
Bone
- necrosis
- fracture
Mouth
- ulceration
- xerostomia
Eyes
- cataracts
Lung
- fibrosis
Hear
- cardiomyopathy
- pericadiafibrosis
Gonads
- infertility
- menopause
Bowel
- strictures
- ulcers
29
Q

Radioresistant cancers

A

Melanoma

Renal cell cancers

30
Q

Cancers predominantly only treated with chemotherapy

A

Mucosal surfaces

  • Head and neck squamous cell
  • Anus and rectal cancers
31
Q

Types of cytotoxic chemotherapy

A

Alkylating agents - form covalent bonds with DNA to impede replication
- depression of bone marrow function, GI upset, increased risk of non-lymphocytic leukaemia
Antimetabolites - block one or more metabolic pathways involved in DNA synthesis
- pyrimidine analogues - fluorouracil
- purine analogues - tigouanine
- depression of bone marrow function, GI epithelial damage, nephrotoxicity, teratogenicity
Cytotoxic antibodies - prevent cell division by different mechanisms
- doxorubicin - prevents DNA unzipping
- dactinomycin - interferes with RNA polymerase
- bleomycin - degrades fully formed DNA
- N+V, myelosuppression, hair loss, fevers, muccositis, pulmonary fibrosis

32
Q

Types of hormonal chemotherapy

A

Drugs antagonise or suppress hormonal action
o Glucocorticoids e.g. prednisolone, dexamethasone – inhibit lymphocyte proliferation
o Oestrogens and anti-androgens – used to suppress growth of prostate tumours
o Anti-oestrogens, e.g. Tamoxifen – competes at oestrogen receptors in breast cancer tissue, preventing oestrogen uptake and therefore reducing rate of tumour growth
o Adrenal hormone synthesis inhibitors (aromatase inhibitors) – used in post-menopausal breast cancer to inhibit sex hormone synthesis
o Progestogens – useful for endometrial neoplasms and renal tumours
o Gonadotrophin releasing hormone analogues/antagonists – act to inhibit gonadotrophin release, preventing its action on tumours and therefore inhibiting tumour growth in advanced breast cancers in pre-menopausal women and prostate cancers
o Somatostatin analogues – relieve symptoms of neuroendocrine tumours,
· Monoclonal antibodies – used for targeted treatment of specific cancers
o Can cause hypotension, chills and fevers, hypersensitivity
· Protein kinase inhibitors – inhibit protein kinases, e.g. tyrosine, which transduce growth signals in rapidly dividing cells

33
Q

Managing side effects of chemotherapy

A

Nausea and vomiting
o Domperidone or metoclopramide in low level nausea and vomiting
o Serotonin antagonists (ondansetron) – better for severe nausea and vomiting
· Extravasation – inflammation caused by leak of white cells into tissue compartments. Seen as pain, redness, blotching and blistering, in serious cases can lead to skin necrosis
o Topical antidotes – e.g. Dimethyl sulfoxide
o Debridement and grafting depending on how damaged the skin becomes
· Bone marrow suppression
o Monitor neutrophil counts and admit for assessment of neutropenic sepsis if neutrophils drop below 0.5x109 cells/L
o Inform patients to go to A+E if they start to feel feverish or unwell during any chemo cycles
o Granulocyte Colony Stimulating Factor can be given to increase circulating volume of white cells if necessary
· Alopecia
o Hair may remain or grow back faster if head is kept cold
· Fertility – many chemotherapeutic agents lead to hypogametogenesis or infertility
o Counselling on this should be given before treatment starts
o Sperm/egg harvest and storage should be offered
o Most chemotherapeutic agents are teratogenic, therefore females should be counselled on contraception
If side effects are causing issues, reduce chemotherapy dose or wait longer between cycles

34
Q

Types of radiotherapy

A

External beam – lasers emitting gamma radiation are fired at the tumour to damage cells, angled to avoid heathy tissues as much as possible
o Curative – given in short doses over a few weeks
o Palliative – large doses all at once to try to shrink tumour
o May be used alongside radiosensitisers – chemotherapy which stimulates the uptake of radiation into targeted tissues to help target radiotherapy further
o Side effects: tiredness, soreness/irritation, diarrhoea if near the rectum, cystitis if near the bladder, impotence, moist desquamation (especially under the breast, avoid by keeping skin clean and moisturised), lymphoedema (reduced drainage if lymph nodes are targeted) xerostomia if near salivary glands, risk of future cancer, nausea and vomiting, myelosuppression, pneumonitis if lung is affected
· Brachytherapy – radiation sources placed in or near the tumour
o Temporary
o Permanent – uses low-dose, long half-life sources
o Systemic – e.g. radioactive iodine taken orally to treat thyroid disease

35
Q

Tumour markers

A

AFP (Alpha-fetoprotein) – liver cancers and germ cell tumours (e.g. testicular cancer)
· B2M (Beta-2-microglobulin) – myeloma, CLL and lymphoma
· Beta-hCG – choriocarcinoma (of trophoblast cells in uterus, e.g. malignant molar pregnancy) and germ cell tumours (e.g. testicular cancer)
· CA15-3 and CA27.29 – breast cancer
· CA19-9 – pancreas, gall-bladder, bile duct and gastric cancers
· CA125 – ovarian cancer
· Calcitonin – medullary thyroid cancer
· CEA (Carcinoembryonic Antigen) – colorectal cancer
· CgA (Chromogranin A) – neuroendocrine tumours
· Fibrin/fibrinogen in the urine – bladder cancer
· Immunoglobulin levels – myeloma
· LDH – melanoma, leukaemia and lymphoma
· PSA – prostate cancer
· Thyroglobulin – thyroid cancer

36
Q

Features of the toxicity bear

A 
Asparagine = neurotoxicity
Cisplatin = ototoxic/nephrotoxic
- tx = amifostine
Vincristine = peripheral neuropathy
Vinblastine = myelosuppression
Bleomycin = pulmonary fibrosis
Doxorubicin = cardiotoxic
- tx = dexrozoxane
Cyclophosphamide = nephro/bladder toxic
- tx = mesna
= SIADH effects
- tx = democlocycline
Methotrexate 
= neprhtoxic
- tx = leucovorin
= myelosuppression
- tx = filgrastim

Yr4 - Cancer Care (12 decks)

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