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Pharmacy 301 > 301 Cancer > Flashcards

301 Cancer Flashcards

1
Q

Epigenetics: what are stable or dynamic changes?

A

Stable: pass on to next generations
Dynamic: response to environmental stimuli

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1
Q

What are epigenetics?

A

Pattern of inheritance in which gene/chromosome is modified temporarily that changes gene expression & function/regulation of DNA, protein or RNA molecules without changing primary sequences

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2
Q

What happens in chromosome inactivation?

A

Allow only one X chromosome to remain active and inactivate the rest of them (forming Barr body from inactive ones)
This is why phenotypes associated with X are less severe than Y

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3
Q

What are Barr bodies?

A

Condensed inactive X chromosomes found in nuclei of female mammals: 1 of 2 C chromosomes randomly inactivated in dosage compensation so 1 Barr body visible in cell nucleus

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4
Q

What is dosage compensation?

A

Process by which organisms equalise expression of genes between members of different biological sexes

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5
Q

Number of Barr bodies:
Normal female
Normal male
Turner syndrome (female)
Triple X syndrome (female)
Klinefelter syndrome (male)

A

XX 1
XY 0
X0 0
XXX 2
XXY 1

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6
Q

What is genomic imprinting?

A

Expression of gene depends on parent sex
Marking of alleles can be changed between generations

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7
Q

What is DNA methylation?

A

Chemical marking process important in genomic imprinting
Methyl (CH3) group added to cytosine in DNA regions needed for gene regulation & expression

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8
Q

Where does DNA methylation take place and what does it result in?

A

Sperm (chromosome X0) or oocyte (not both)
Gene expression inhibition (silences genes)

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9
Q

What are classical genetic controlled by?

A

Promoters, enhancers or proteins binding sites that are present or absent in DNA sequences

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10
Q

What is the difference between genetic & epigenetic regulation?

A

E: do not involve change to DNA sequence or mutations to sequence
Implies modification of DNA & proteins, without changing DNA sequence
Regulation at level above genetic mechanism regulation

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11
Q

What is model organism in epigenetics?

A

Different advantage & all important for learning about processes & mechanisms involved in epigenetic regulation

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12
Q

Saccharomyces cerevisiae (budding yeast) has helped what?

A

Elucidate chromosome structure & telomere silencing (regulates gene transcription near telomeres - prevents premature aging & aging-related diseases)

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13
Q

Protozoan Tetrahymena thermophilia is used for what?

A

Study of RNAipathway that functions gene silencing

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14
Q

What is a classic genetic model used for epigenetic research?

A

Drosophila melanogaster

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15
Q

What is a plant model with considerable epigenetic mechanisms like mammals

A

Arabidopsis thaliana

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16
Q

When are mice used in epigenetic research?

A

Embryology

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17
Q

What are biological applications of epigenetics?

A

Control expression of embryonic development genes
Erasure & re-establishment of DNA methylation
Genetic imprinting
X-chromosome inactivation
Stem cell development
Somatic cell differentiation
Production of differentiated cells from adult stem cells & specific cell types

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18
Q

What is found to correlate with cancer?

A

DNA methylation biomarkers
Cancer tumour suppressor genes show hypermethylation but also hypomethylation are expressed in other cancers

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19
Q

What is not involved in epigenetic alterations to genome?

A

Change in nucleotide sequence
Managing and controlling alterations plays role in cancer prevention and treatment

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20
Q

Examples of epigenetic mechanisms applied in different cancer types

A

Silencing tumour suppressor
Activation of oncogenes
Histone modifications

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21
Q

Epigenetic therapy: tumour suppressor genes

A

Decrease of tumour growth
Induction of apoptosis
Suppression of invasion & metastasis

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22
Q

Epigenetic therapy:
Stem cell genes
miRNAs regulating stem cell genes in CICs

A

Decrease of self-renewal or survival of CICs
Differentiation of CICs

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23
Q

Epigenetic therapy:
Tumour suppressor genes
Drug response genes

A

Resensitisation to chemotherapy

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24
Q

FDA approved epigenetic chemotherapy

A

Azacitidine (Vidaza)
Decitabine (Dacogen)
Vorinostat (Zolinza)
Romidepsin (Istodax)

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25
Q

Epigenetic therapy: Azacitidine (Vidaza)

A

Make genes fight cancerous cells when given at low doses, shows effectiveness against certain lung cancers

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26
Q

Epigenetic therapy: Azacitidine (Vidaza)

A

Make genes fight cancerous cells when given at low doses, shows effectiveness against certain lung cancers

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27
Q

Epigenetic therapy: decitabine (Dacogen)

A

Treats myelodysplasia (affects blood cell production in bone marrow) and leukaemia

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28
Q

Epigenetic therapy: Vorinostat (Zolinza)

A

Treats immune system cancer (cutaneous T-cell lymphoma)

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29
Q

Epigenetic therapy: romidepsin (Istodax)

A

Epigenetic injection therapy (like Vorinostat and romidepsin)
Treats peripheral T-cell lymphoma in patients who have received 1+ prior treatment

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30
Q

Epigenetic therapy: romidepsin (Istodax)

A

Epigenetic injection therapy (like Vorinostat and romidepsin)
Treats peripheral T-cell lymphoma in patients who have received 1+ prior treatment

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31
Q

What is carcinogenesis?

A

Molecular process where cancer develops

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32
Q

External, lifestyle and environmental factors in carcinogenesis

A

Ex: chemicals, viruses, diet & radiation
Env: chemicals (air pollutants, asbestos)
Life: diet, smoke, alcohol, direct sun exposure

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33
Q

What is cancer development?

A

Multi-stage process involving damage to genetic material of cells (DNA)
Damage of genes that regulate normal cell growth and division

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34
Q

What are carcinogens?

A

Agents causing cancer
Classified as genotoxic or nongenotoxic (epigenetic)

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35
Q

What are genotoxins?

A

Cause irreversible genetic damage (mutations) by binding to DNA

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36
Q

Examples of genotoxins

A

Chemical agents like N-methyl-N-nitrosourea or non-chemical agents UV light

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37
Q

Why can viruses act as carcinogens?

A

Interact with DNA (HBV and liver and HPV and cervix)

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38
Q

Stages of carcinogenesis

A
  1. Initiation
  2. Promotion
  3. Transformation
  4. Progression
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39
Q

Stages of carcinogenesis: initiation

A

Involve random change in genetic makeup of cell
>1 agent acts together as carcinogens
Carcinogen interacts with DNA causing damage at gene location that regulates cell growth
If cell repair systems do not occur, cell may turn cancerous

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40
Q

What is the 1st stage in neoplastic development?

A

Initiation stage of carcinogenesis

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41
Q

Stages of carcinogenesis: progression

A

Malignant conversion stage
Irreversible
Changes in structure of genome, increased growth rate
Invasiveness
Metastatic capability
Biochemical changes & neoplastic cells born
Expansion of tumour cells
Genetic material of tumour is more fragile and go through additional mechanisms

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42
Q

Stages of carcinogenesis: promotion

A

Initial cell damage rarely results in cancer due to cell mechanisms to repair damaged DNA
Reversible and revocable if stimulus stops
Promoted not always carcinogen but enhances carcinogenicity
Continually controlled through environmental alterations
Cigarette smoke, bile acids & chemical pollutants involved in promotion

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43
Q

When does cancer occur?

A

When tumour suppressor genes inactivated and oncogenes are activated

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44
Q

What are tumour suppressor genes associated with?

A

Healthy cell activities like cell growth, cell differentiation & apoptosis

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45
Q

What do tumour suppressor genes produce?

A

Proteins that inhibit cell reproduction during inappropriate growth times (control cell division during repair times)

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46
Q

What are proto-oncogenes?

A

Altered version of normal genes, regulate cell growth and survival

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47
Q

What activate proto-oncogenes?

A

Mutations

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48
Q

Mechanism of oncogene action

A

Cell surface receptors
Intercellular signal transduction pathways
DNA-binding nuclear protein (transcription factor)
Cell cycle proteins (cyclins & cyclin-dependent protein kinases)
Inhibitors of apoptosis

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49
Q

What do oncogenes trigger?

A

Signal transduction (cascade of biochemical signals)
These signals control genes that regulate cell growth and division

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50
Q

What is important for cancer to occur?

A

Activation of oncogenes and inactivation of tumour suppressor genes

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51
Q

What tumour suppressor genes are associated with cell growth and differentiation?

A

P53 and DCC

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52
Q

What are the most common mutations seen in humans?

A

Mutations that inactivate tumour suppressor gene p53

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53
Q

Colon carcinogenesis

A
  1. Mutations of APC: sometimes inherited, leads to dysplasia or polyp formations on mucous membrane surface
  2. DCC: subsequent mutations lead to late adenoma and then carcinoma
  3. Changes in p53 genes: progressive changes seen in colonic epithelium as polyps remain dormant for years
  4. DNA microsatellite instability (MSI): hyper mutable phenotype caused by loss of DNA repair activity
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54
Q

p53 mutations lead to what?

A

Over expression of oncogenes and deletion of anti-oncogenes and DNA repair gene

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55
Q

What does APC stand for?

A

Adenomatous polyposis coli

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56
Q

What does DCC mean?

A

Deletion in colon cancer gene

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57
Q

What are the tumour markers for:
Lung cancer
Liver cancer
Prostate cancer
Testicular cancer
Breast cancer
Stomach cancer
Colon cancer
Pancreatic cancer
Ovarian cancer

A

CA125, CEA
AFP
PSA
AFP, HCG
CA125, CEA, HER2
CEA
CEA
CA125, CEA
CA125, CEA

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58
Q

What are tumour markers and can be detected where?

A

Substances produced by cells (normal or cancer) of body in response to cancer or benign conditions
Blood, urine, stool, tumour tissue and other body fluid samples

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59
Q

Benefits of tumour markers in cancer care

A

Used in highly sensitive and specific screening tests for early detection
Elevated levels suggest but do not diagnose
Combine with other tests for diagnosis
Used to manage some types of cancer
Helps doctors know stage & suitable therapy
Determines whether tumour responds to treatment

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60
Q

Limitations of tumour markers in cancer care

A

Tumour markers may increase in non-cancerous conditions
Not all patients have elevated tumour markers
Tumour markers not identified for all types of cancer

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61
Q

Alpha-fetoprotein (AFP):
Cancer types
Tissue analysed
How used?

A

Liver, germ cell tumours
Blood
Diagnose liver cancer and follow treatment response, assess stage, prognosis and response to treatment to germ cell tumours

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62
Q

Beta-2-microglobulin (B2M):
Cancer types
Tissue analysed
How used?

A

Multiple myeloma, chronic lymphocytic leukaemia and some lymphomas
Urine or blood
Assess stage, prognosis and treatment response

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63
Q

Mitomycin and fluorouracil are categorised under which groups and what are the major S/Es of these cytotoxic agents?

A

M: antineoplastic antibiotic, works by cross-linking DNA, inhibiting DNA synthesis
Bone marrow suppression, renal toxicity, interstitial pneumonitis and risk of extravasation leading to severe tissue damage
5FU: antimetabolite, inhibits thymidylate synthase, disrupting DNA synthesis
Myelosuppression, GI toxicity (mucositis and diarrhoea), hand-foot syndrome and potential cardiotoxicity

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64
Q

What is extravasation and which cytotoxic agents can cause extravasation?

A

Accidental leakage of vesicant or irritant drug into surrounding tissue during IV admin., vesicants are agents that cause tissue damage & necrosis
Mitomycin and other vesicants (anthracyclines - doxorubicin) high risk of causing tissue damage, 5FU less vesicant but can cause irritation

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65
Q

What are the symptoms of extravasation?

A

Pain, sudden pain or stinging, swelling or oedema, redness, blisters or sores at injection site
Slowed flow, infusion pump may alarm, absence of blood return

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66
Q

Treatment for patients with rectal cancer with extravasation from adjuvant IV push chemotherapy

A

Immediately stop infusion, leave needle in place and aspirate
Specific to mitomycin - use cold compress reducing local inflammation, administer topical dimethyl sulfoxide (DMSO)
Pain relief with analgesics, monitor for necrosis or tissue damage signs

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67
Q

What is irinotecan and what does it do?

A

Semisynthetic derivatives plant alkaloid, inhibit topoisomerase I
Creates single-strand breaks in DNA during replication, preventing DNA re-ligating so double-strand breaks and cell death

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68
Q

What are the common toxicities from irinotecan?

A
  1. Diarrhoea - early-onset (during/after admin.)
  2. Myelosuppression includes neutropenia, leukopenia, anaemia & thrombocytopenia
  3. N + V frequent
  4. Fatigue
  5. Alopecia, anorexia & abdo. pain
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69
Q

A patient on combined chemotherapy has both ventral surface on his tongue and floor of his mouth appears erythematous and several discrete lesions are present in both areas

A

New onset generalised burning, pain, erythema & discrete lesions on ventral tongue surface and mouth floor due to oral mucositis
Common in chemotherapy given concurrently due to therapies damaging rapidly dividing epithelial cells in oral mucosa, leading to inflammation, ulceration & pain

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70
Q

Which cytotoxic drugs can cause oral mucositis?

A

5-FU - affects rapidly dividing cells in GI tract, including oral mucosa
Methotrexate - another antimetabolite can lead to severe mucositis
Irinotecan - cause GI toxicity, may lead to oral mucositis
Doxorubicin and other anthracyclines - lead to mucositis as part of their toxicity profile

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71
Q

What should be advised for oral mucositis in cancer patients?

A

Rinse mouth frequently & effective teeth brushing with soft brush 2-3 times daily, in fluorouracil suck ice chips during short infusions to help
Generally self-limiting but poor oral hygiene becomes focus for blood-borne infection

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72
Q

What toxicities might be expected in concurrent (carboplatin, topotecan and etoposide) chemotherapy?

A

Myelosuppression
Neutropenia (increased infection risk)
Thrombocytopenia (increased bleeding)
Anaemia (fatigue, SOB)
GI toxicity
N + V
Diarrhoea (dehydration & electrolyte imbalances)
Mucositis
Fatigue
Alopecia
Renal & hepatic toxicity
Hypersensitivity
Radiation-specific toxicities
Skin irritation
Oesophagitis

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73
Q

Which one of chemotherapeutic agents can cause N + V and how do you classify emetogenic potential?

A

Cisplatin most associated, considered high emetogenic potential, meaning significant risk (>90%) of N + V without adequate prophylaxis, fluorouracil has low to minimal emetogenic risk

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74
Q

How should N + V induced chemotherapy be managed and what will be your recommendations for this patient?
- Prevention strategy for high emetogenic risk (cisplatin-based regimen)
- Antiemetic recommendations
- Breakthrough and rescue therapy

A

Acute CINV - occurs within 24 hrs
Delayed CINV - 24 hrs+
Acute phase - 5HT3 antagonist (palonosetron - longer 1/2 life), NK1 antagonist (aprepitant), corticosteroid (dexamethasone) and olanzapine
Additionally add prochlorperazine, lorazepam or metoclopramide for breakthrough N + V

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75
Q

What is cisplatin nephrotoxicity?

A

Cisplatin accumulates in renal tubular cells, causing damage to kidneys, manifests as reduced GFR
Repeated exposure over multiple cycles leads to cumulative kidney injury as seen with drop in creatinine clearance

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76
Q

Cisplatin and hypomagnesemia

A

Cisplatin causes renal magnesium wasting by damaging the renal tubules, leading to decreased reabsorption of magnesium and subsequent hypomagnesemia, can cause hypoglycaemia and unprovoked seizures

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77
Q

What measures should be taken to prevent cisplatin nephrotoxicity?

A
  • Pre and post hydration
  • Diuretic use like mannitol (good urine flow, only in well hydrated patients)
  • Electrolyte replacement (Mg & K)
  • Dose adjustment (based on renal function)
  • Amifostine (cytoprotective agent, S/E of hypotension)
  • Renal function tests and urine output (monitor serum creatinine, creatinine clearance and electrolytes)
78
Q

What is breast cancer?

A

Breast made up of fat, connective tissue, gland tissue & ducts
Changes during differing times of the month
Younger women have more glandular tissue than fat, this changes as age increases, glandular tissue is replaced with fat tissue

79
Q

Types of breast cancer: classification by tissue

A

Ductal carcinoma - affects milk ducts (most common)
Lobular carcinoma - affects lobules (milk-producing parts)

80
Q

Types of breast cancer: classification by invasiveness

A

Noninvasive (in-situ) carcinoma - cancer remains in ducts/lobules e.g. ductal in-situ (DCIS) and lobular in-situ (LCIS)
Invasive carcinoma - cancer spreads to other parts of breast

81
Q

Types of breast cancer: classification by hormones/genes

A

ER-positive breast cancer - sensitive to oestrogen
HER2-positive breast cancer - caused by HER2 gene, linked to cell growth and repair

82
Q

How does breast cancer spread?

A

Collection of lymph nodes around breast that form part of lymphatic system
Lymph nodes collect waste products from nearby and drain into lymph vessels
Cancer vessels can break off of tumour & collect in lymph nodes

83
Q

Breast cancer epidemiology

A

Breast cancer is most common cancer in women
Accounts for 31% of malignancies in women
1 in 7 women will be affected by breast cancer
Less common in males, 370 diagnosed each year
4th most common cause of cancer deaths in UK
Accounts for 11,400 deaths a year in UK (2014-2016), fallen by 38% since 1970

84
Q

What is klinefelter syndrome and its relation to breast cancer risk?

A

Genetic condition increasing risk of men developing breast cancer, man born with extra X so XXY makeup, leads to lower testosterone and higher oestrogen, increasing breast cancer risk

85
Q

Survival rates for breast cancer

A

Net survival rate in women increasing
Survival rates have doubled in last 40 years
10 year survival rate increased from 40% in 1970 to 80% today

86
Q

Breast cancer aetiology

A
  • Age
  • Diet
  • Exposure to exogenous oestrogens (HRT)
  • Benign breast disease
  • Exposure to radiation
  • Duration of exposure to oestrogens
  • Family history (risk x2 i 1st degree relative has it), links between breast and ovarian, endometrial and colon cancer
87
Q

What are the 4 common genes that cause breast cancer?

A

BRCA1
BRCA2
CHECK2
TP53
Mutations in these genes increases lifetime risk up to 80%

88
Q

Can HRT be taken in breast cancer?

A

All types of systemic (oral or transdermal) HRT increase risk of breast cancer after 1 year of use, risk is higher in oestrogen-progestogen HRT than oestrogen-only
Longer duration of HRT use (but not the age HRT is started) further increases risk

89
Q

Signs and symptoms of breast cancer

A
  • Breast lump
  • Breast pain or tenderness
  • Dimpling, erythema, puckering
  • Nipple changes or discharge
  • Any other unexplained changes to skin, shape or size of breast
90
Q

NHS breast screening programme

A

Women registered with GP between 50-71 automatically invited for free mammogram every 3 years
Over 71 may book free appointment (higher risk)

91
Q

Breast cancer diagnosis and investigations

A

Mammography
Full clinical examination
Ultrasonography
Aspiration cytology - extracts cancer cells
Biopsy of tumour

92
Q

Why ultrasonography in younger women under 50?

A

More fatty tissue in older women, in young women tissue is dense so cannot be seen with mammography

93
Q

Staging and performance status in breast cancer

A

TMN classification
T - primary tumour, T0 (no detectable tumour), T1 (<2cm), T2 (2-5cm), T3 (>5cm)
M - metastatic, M0 (no metastases), M1 (spread to distant organs)
N - nodal N0 (no nodes involved), N1 (mobile axillary nodes), N2 (fixed axillary nodes), N3 (involved supra or intraclaviular nodes)

94
Q

Breast cancer diagnosis stage assessment:
Early/locally advanced
Advanced/metastatic

A
  1. ER/PR positive - endocrine therapy (tamoxifen or aromatase inhibitors), add chemotherapy if high risk
    HER2 positive - chemotherapy + trastuzumab, consider pertuzumab if needed
    Triple negative - chemotherapy, anthracycline or taxane-based
  2. ER/PR positive - endocrine therapy, CDK4/6 inhibitors or chemotherapy
    HER2 positive - chemotherapy + targeted therapy
    Triple negative - chemotherapy, sequential single agents
95
Q

Surgery options for breast cancer:
Tumours <5cm
Tumours >5cm

A
  1. Wide local excision
  2. Mastectomy with axillary dissection
96
Q

Tumour <5cm, what surgery can be used to remove in breast cancer?

A

Not fixed surgery can be used to remove lump (wide local excision)

97
Q

What surgery is used to remove lymph nodes under the arm in breast cancer?

A

Sentinel node biopsy, if positive –> axillary nodes removed and patients have adjuvant chemotherapy

98
Q

Advanced breast cancer:
Older women
Younger women
Reconstructive surgery (at time of surgery or afterwards)

A
  1. Options is hormonal therapy if ER/PR positive
  2. Neoadjuvant chemotherapy to reduce size of tumours
    Followed by surgery and radiotherapy
  3. Think of psychological impact
99
Q

Metastatic breast cancer

A

Depends upon age and site of metastases
Metastases to skin & bone:
- Preferred treatment is hormonal therapy provided ER/PR positive e.g. tamoxifen
- Approx. 70% women >70 will respond
In younger women:
- Oestrogen mainly from ovaries
- Preferred treatment removal of ovaries

100
Q

What does tamoxifen do?
What do aromatase inhibitors do?

A
  1. Binds to oestrogen receptors & prevents oestradiol from binding
  2. Binds & inhibits aromatase enzymes in peripheral tissue that converts androgens into oestrogen in peripheral tissue (post-menopausal) role to play in palliative patients where tamoxifen fails
101
Q

Where does oestrogen occur in young and older women?

A

Younger - one ovary
Older - peripheral tissues

102
Q

Triple negative breast cancer

A

Responds to chemotherapy with cisplatin in combo with other drugs e.g. PARP inhibitors (disable DNA base excision repair)
PARP inhibitors end in ‘parib’ e.g. Olaparib
HER2 positive patients - treatment include trastuzumab
Monoclonal antibody
Give IV or SC (less treatment needed in thighs)
Risk of sensitivity reactions monitor 6 hrs after 1st dose
Common S/Es: injection site reactions, hypersensitivity, fever, BP changes, headache

103
Q

Types of cytotoxic drugs

A

Taxanes - paclitaxel, doxcetaxel
EC - epirubicin & cyclophosphamide
TC - doxcetaxel & cyclophosphamide
AC - doxorubicin & cyclophosphamide
Carboplain
Capecitabine

104
Q

What is gastrointestinal cancer?

A

Broad term for cancers affecting GI tract
Oesophageal, pancreatic, gastric (stomach), hepatobiliary & colorectal cancer

105
Q

What is colorectal cancer?

A

Cancer that starts in the colon or rectum

106
Q

Colorectal cancer epidemiology

A

Commonly found in both men & women
4th most common cancer for both men & women
Accounts for 15,609 deaths annually
41,581 affected annually
5 year survival rate in F is 56% & M is 54%

107
Q

Colorectal cancer aetiology

A

Incidence increases 50+, median age is 70
Affects men & women equally
Diet, smoking, excess alcohol consumption, obesity, inactivity, CD and UC

108
Q

Why does red meat and low fibre have an increased risk in colorectal cancer?

A
  1. Chemical haem which is broken down in gut, N-nitroso chemicals are formed & found to damage cells lining bowel
  2. High fibre binds carcinogens to stool & expels them from body, good bacteria in colon convert fibre into short-chain fatty acids (reduce ability of cells in intestine to become cancerous)
109
Q

Modifiable risk factors of colorectal cancer

A

Red and processed meat
Obesity
Alcohol
Smoking

110
Q

Fixed risk factors of colorectal cancer

A

Older age
Male sex
Family history
IBD - risk increases with duration of disease
Diabetes

111
Q

What are the two conditions that lead to development of colorectal cancer?

A
  1. Hereditary non polyposis colorectal cancer (HNPCC)
  2. Familial adenomatous polyposis (FAP)
112
Q

What is hereditary non polyposis colorectal cancer (HNPCC)?

A

Inherited disorder increasing risk of colorectal cancer
Symptoms of abdo. pain, bloating, appetite loss, bloody stools, fatigue & weight loss
Treatment - surgery, chemotherapy, immunotherapy
Prevention - regular colonoscopies

113
Q

What is familial adenomatous polyposis (FAP)?

A

Genetic condition causes hundred or thousands of non-cancerous polyps to develop in colon an rectum
Polyps left can become cancerous caused by adenomatous polyposis coli (APC) gene mutation which is inherited from parent

114
Q

Signs and symptoms of colorectal cancer

A

Blood in stool
Changes to bowel habits
Weight loss
Abdo. pain
Straining when using toilet
Lump at back passage can be felt by Dr

115
Q

Diagnosis and investigations in colorectal cancer

A
  • Full Hx
  • Exam including rectal
  • Proctoscopy & sigmoidoscopy
  • Blood test - FBC, renal & liver function tests
  • Chest X rays
  • Barium enema or colonoscopy (narrowing of colon like an apple core)
116
Q

Screening for colorectal cancer

A

Everyone 60-74 year old
Program expanding to include 50-59 year old by 2025
Involves home kit test called faecal immunochemical test (FIT)
Faecal sample is collected & tested for blood, blood in stool sample can indicate polyps or cancer & further testing needed
Everyone 60-74 registered with GP sent kit every 2 years

117
Q

Colorectal cancer staging

A

Determines size of tumour, dissemination of disease & allow us to determine treatment options
T - tumour
N - node
M - metastases

118
Q

Colorectal cancer number staging system and Dukes stages

A

Stage 0, 1, 2 a/b, 3 a/b/c, 4
Dukes divided into stage A (early stage) to D (advanced colorectal cancer)

119
Q

Treatment options for colorectal cancer

A

Surgery - depends on operability & size of tumour
Complications include lack of bladder control, ureteric tears, sexual dysfunction in males

120
Q

Metastatic disease in colorectal cancer:
Regimens
Monoclonal antibodies

A

5-FU based treatment in combo with folinic acid (improve remission rates)
Regimens:
FOLFOX (oxaliplatin added to 5FU)
FOLFIRI (irinotecan added to 5FU)
CAPOX (XELOX)
MA have been added to regimens and shown to prolong life 9-18 months
Bevacizumab, cetuximab, panitumumab

121
Q

What is the difference between invasive and in situ cancers?

A

Invasive - spread to nearby tissues
In situ - contained in original tissue

122
Q

Monoclonal antibodies in cancer

A

Seeks out cancer cell proteins
Monoclonal antibodies bind to proteins
Antibodies signal to immune cells
Immune cells arrive & punch holes in cancer cell

123
Q

What factors can influence the survival of a cancer patient?

A

Stage
Grade
Hormone receptor status
HER2 status - positive is more aggressive
General health
Lifestyle
Socioeconomic factors
Inflammatory cytokines
Tumour size, nodal status, mitotic index, lymphovascular invasion gene profiling, comorbidity, local & regional recurrence, metastases & second cancer

124
Q

What factors are associated with increased risk of developing colorectal cancer in patient with IBD?

A

Disease duration, extent and family history

125
Q

List some ethical issues commonly faced in practice with cancer diagnoses

A

Screening
Religion, culture, socioeconomic status
Major surgery
Heredofamilial cancer risk (occurs in 1+ family member)
Overcome with advanced care planning, communication and family surrounding

126
Q

How long for a breast cancer referral process to take place?

127
Q

Types of cancer induced nausea and vomiting

A
  1. Chemotherapy induced nausea & vomiting
  2. Radiotherapy-induced nausea & vomiting
128
Q

Chemotherapy induced nausea and vomiting: patient factors

A
  1. Female
  2. > 50
  3. Previous episodes of chemotherapy-associated emesis
  4. History of motion sickness &/or nausea for pregnancy
  5. Minimal alcohol consumption
129
Q

Nausea and vomiting: acute emesis

A

Less than 24 hrs after chemo administration
Usually peaks after 5-6 hrs

130
Q

Nausea and vomiting: delayed emesis

A

1 to 7 days after treatment
Usually peaks after 48-72 hrs and can last 6-7 days

131
Q

Nausea and vomiting: anticipatory emesis

A

Prior to treatment

132
Q

Nausea and vomiting in cancer: what to consider

A

Emetogenic potential of regimen
Risk of delayed N + V
Individual patient factors

133
Q

High emetogenic risk >90%: IV agents

A

Camustine
Carboplatin (>4 AUC)
Cisplatin
Cyclophosphamide (>1500 mg/m^2)
Cyclophosphamide with anthracycline in breast cancer
Dacarbazine
Streptozocin

134
Q

High risk emetogenic (>90%): oral agents

A

Busulfan
Procarbazine

135
Q

High emetogenic risk: acute emesis management (day 1)

A

Pre treatment with:
Substance P antagonist (NK1 antagonist) - aprepitant PO or fosaprepitant IV or netupitant PO
PLUS
Dexamethasone 12mg (oral or IV) daily
PLUS
5HT3 receptor antagonist - ondansetron (oral/IV), granisetron (oral/IV), palonosetron (IV)

136
Q

High emetogenic risk: acute emesis management (day 1)

A

Pre treatment with:
Substance P antagonist (NK1 antagonist) - aprepitant PO or fosaprepitant IV or netupitant PO
PLUS
Dexamethasone 12mg (oral or IV) daily
PLUS
5HT3 receptor antagonist - ondansetron (oral/IV), granisetron (oral/IV), palonosetron (IV)

137
Q

High emetogenic risk: delayed emesis (from day 2)

A

Prophylactic treatment
Continue with dexamethasone (PO or IV) 8mg daily for 3 days post chemotherapy
Once daily if also using aprepitant/fosaprepitant
Twice daily without aprepitant/fosaprepitant
Omit dexamethasone when corticosteroids are included as part of the chemotherapy or premedication regimen, or when the patient is already on corticosteroids equivalent to the dose of dexamethasone that is required

138
Q

Moderate emetogenic risk (30-90%): IV agents

A

Azacitidine
Carboplatin (<4 AUC)
Doxorubicin
Ifosfamide
Melphalan
Methotrexate >250mg/m^2
Oxaliplatin

139
Q

Moderate emetogenic risk (30-90%): oral agents

A

Cyclophosphamide
Lomustine
Temozolamide

140
Q

Moderate emetogenic risk: acute emesis management (day 1)

A

Pre-treatment with
Dexamethasone PO or IV - dose 8mg
PLUS
Palonosetron IV (5HT3 antagonist) or ondansetron

141
Q

Moderate emetogenic risk: delayed emesis management (from day 2)

A

Prophylaxis with
Dexamethasone (PO or IV) 8mg once daily (or in divided doses) for 2 days post chemotherapy
OR
5HT3 antagonist
Omit dexamethasone when corticosteroids are included as part of chemotherapy or premedication regimen, or when patient is already on corticosteroids equivalent to dose of dexamethasone that is required

142
Q

Low emetogenic risk: acute emesis management (day 1)

A

Pre-treatment with a single dose of:
Dexamethasone (PO or IV) 4-8mg
OR
Metoclopramide 10mg (PO or IV) PRN
OR
Prochlorperazine 10mg PO (12.5mg IV) PRN
(OR 5HT3 antagonist OR domperidone PO ) (AMH)

143
Q

Low emetogenic risk: delayed emesis (from day 2)

A

Antiemetics for delayed emesis are not routinely required

144
Q

Minimal emetogenic risk: emesis management

A

No antiemetic should be routinely administered before chemotherapy in patients with history of N + V
If patients experience N + V, consider using low antiemetic prophylaxis regimen

145
Q

Cytotoxic agent common side effects

A
  • N + V
  • Mucositis
  • Diarrhoea
  • Alopecia
  • Myelosuppression
  • Tumour lysis syndrome
  • Infertility
  • Secondary malignancies
146
Q

Surgery in early breast cancer:
Tumour size: <5cm and not fixed
>5cm

A
  1. Lumpectomy -> lymph node biopsy
  2. Mastectomy -> axillary dissection
147
Q

Adjuvant therapy post-surgery - breast cancer

A
  • Radiotherapy
  • Endocrine therapy
  • Cytotoxic drugs
  • Immunological therapy
  • Targeted therapies
148
Q

Radiotherapy in breast cancer

A
  • Usually have adjuvant
  • Pre radiotherapy risk of reoccurrence can be as much as 40-60%
  • Post radiotherapy risk reduces to 4-6%
  • Radiotherapy given over 6 weeks, must attend hospital everyday
149
Q

Breast cancer radiotherapy S/Es

A
  • Mild burning of skin
  • Damage to brachial nerve
  • More old fashion machines & plans can cause damage to coronary blood vessels
  • Rarely formation of 2nd cancer
150
Q

Adjuvant hormonal therapy in premenopausal women

A

80% breast cancers are ER positive, use oestrogen receptor modulator tamoxifen
2 classes - ERa & ERb
Current standard tamoxifen 20mg every day for 5 years
S/Es menopausal symptoms, thromboembolic disease

151
Q

Adjuvant hormonal therapy in postmenopausal women

A

Current standard to give sequential tamoxifen followed by aromatase inhibitors (anastrozole)
Given a total of 5 years (tamoxifen 3 years, aromatase 2 years)
S/Es: osteoporosis, alopecia, decreased appetite

152
Q

What are the key mechanisms of endocrine therapy in breast cancer for premenopausal women?
Mechanism
Treatment

A
  1. Hypothalamus releases GnRH → Stimulates pituitary to release gonadotrophins (FSH & LH) → Ovaries produce estrogen and progesterone
  2. Tamoxifen: Binds to estrogen receptors (ERα) and prevents estradiol binding
    Ovarian suppression: Irradiation, surgical oophorectomy, or LHRH agonists (e.g., goserelin)
153
Q

What are the key mechanisms of endocrine therapy in breast cancer for postmenopausal women?
Mechanism
Treatment

A
  1. Adrenal glands produce androgens, which are converted to estrogens in peripheral tissues (adipose, liver, muscle)
  2. Aromatase inhibitors: Block peripheral estrogen production
    Tamoxifen: Prevents estradiol binding to ERα
154
Q

Why may a patient not use tamoxifen and fluoxetine at the same time?

A
  1. Tamoxifen is a prodrug
  2. Fluoxetine could reduce action and effectiveness of tamoxifen in preventing growth of breast cancer
  3. Is a strong inhibitor of enzyme CYP2D6 which is responsible for converting tamoxifen into its active metabolite, endoxifen
155
Q

What drugs interact with tamoxifen and why?

A

Antidepressants such as fluoxetine, paroxetine, duloxetine & bupropion
Is a prodrug, it is converted to its active metabolite (endoxifen) by cytochrome P450 enzyme

156
Q

Breast cancer adjuvant chemotherapy example and addition of taxanes do what?

A
  1. FEC-T (fluorouracil, epirubicin, cyclophosphamide & docetaxel)
  2. (Docetaxel or paclitaxel) Increase efficacy of treatment
157
Q

Fluorouracil MOA

A
  • Inhibits thymidylate synthetase activity, preventing thymidylate formation from uracil, inhibits DNA and RNA synthesis & cell death
  • Incorporated into RNA in place of UTP, producing a fraudulent RNA interfering RNA processing & protein synthesis
  • Blocks enzyme that converts cytosine nucleotide into deoxy derivative
158
Q

Fluorouracil most common S/Es and route

A

Diarrhoea, N + V, constipation, loss of appetite, sores in throat, swelling at site, tingling of limbs
IV

159
Q

Epirubicin MOA

A
  • Forms complexes with DNA by intercalation between base pairs
  • Inhibits topoisomerase II activity by stabilising DNA-topoisomerase II complex preventing re-ligation
  • Inhibits DNA and RNA & protein synthesis
160
Q

Epirubicin S/Es and route

A

Bruising, bleeding gums and nose, breathlessness, alopecia, N + V, fever, cough
IV

161
Q

Cyclophosphamide MOA

A
  • Active metabolites alkylate cellular macromolecule, creating covalent linkages that prevent their dissociation
  • Preventing cell division and perturbs gene expression
162
Q

Cyclophosphamide S/Es and route

A

Bruising, bleeding, haematuria, N + V, diarrhoea, anorexia, mouth sores
Oral, IV

163
Q

Docetaxel MOA

A
  • Reversibly binds to microtubulin with high affinity in 1:1 stoichiometric ratio, allowing cell division prevention & promote cell death
  • Inhibits microtubule depolymerisation
164
Q

Docetaxel S/Es and route

A

Infections, alopecia, muscle or joint pain, fluid retention, N + V, diarrhoea
IV

165
Q

Adjuvant immunological therapy in breast cancer:
EGFR2
Target for?
HER2 positive patients
Trastuzumab

A
  1. 25% breast cancers will express EGFR2
  2. Target monoclonal antibodies (trastuzumab)
  3. Patient HER2 positive given adjuvant trastuzumab (Herceptin)
    Given over 12-18 months
  4. Toxicity significant, particularly cardiac effects (heart failure)
166
Q

Surgery for early colorectal cancer

A

Most common treatment
Includes local resection (surgery to remove part of small bowel)

167
Q

Adjuvant treatment for colonic cancer and Dukes A, B and C disease

A
  1. A: no need for adjuvant
  2. B: very little benefit
  3. C: should receive adjuvant
168
Q

Example of adjuvant treatment for colorectal cancer

A

FOLFOX
5FU
Folinic acid
Oxaliplatin - monitor renal function
Given every fortnight for 6 months

169
Q

Radiotherapy in rectal cancer

A

Receive radiotherapy prior to operation
Alternative: maybe given following surgery reduces risk of pelvic reoccurrence by 5-10%
Patient with advanced tumour (T3 and T4) can receive neoadjuvant chemoradiotherapy prior to surgery - complete remission in 70%

170
Q

Alkylating agents:
MOA

A

Attach alkyl groups to DNA
Allowing crosslinking of base pairs
Damaging DNA

171
Q

Types of alkylating agents

A

Cyclophosphamide, ifosfamide, melphalan

172
Q

Side effects of alkylating agents

A

Myelosuppression (drop in WBC, Hb, crit)
N + V
2ndary malignancies
Infertility/impaired fertility
Haemorrhagic cystitis

173
Q

Atypical alkylating agents: MOA

A

Platinum compounds covalently bind purine DNA bases

174
Q

Examples of atypical alkylating agents and S/Es

A

Cisplatin: nephrotoxicity and N + V
Carboplatin: thrombocytopenia
Oxaliplatin: cold sensitivity
(All: peripheral neuropathies, paresthesia)
Nitrosoureas: BCNu, CCNu (ause pulmonary toxicity, phlebitis, CNS)

175
Q

Antimetabolites: MOA

A

Inhibit DNA replication or repair by mimicking normal cell compounds, S phase specific

176
Q

Antimetabolites: folate inhibitor methotrexate

A

Inhibits DHFR, prevents THF regeneration
Adjuvant leucovorin to protect healthy cells (adjuvant)

177
Q

Antimetabolite side effects:
Folate inhibitor (methotrexate)
Pyrimidine inhibitors
5-FU
Capecitabine
Cytarabine

A
  1. Mucositis, myelosuppression
  2. Myelosuppression at bolus, mucositis & diarrhoea at continuous dose
  3. Hand-foot syndrome
  4. Conjunctivitis & cerebellar neural defects
178
Q

Antimetabolites: pyrimidine inhibitors
5-fluorouracil
Capecitabine
Cytarabine

A
  1. Inhibits thymidylate synthetase
  2. Oral prodrug of 5-FU
  3. (AraC) is DNA chain terminator
179
Q

Microtubule targeting agents: MOA

A

Drugs inhibit mitosis, specifically M phase

180
Q

Microtubule targeting agents: vinca alkaloids MOA
Examples
S/Es

A

Destroy microtubules, preventing function
Vincristine, vinblastine & vinorelbine
Peripheral neuropathy, myelosuppressive, fatal if given intrathecally

181
Q

Microtubule targeting agents: taxanes
MOA
Examples
S/Es

A

Stabilise microtubules, preventing function
Paclitaxel & docetaxel
Myelosuppression, peripheral neuropathies, hypersensitivity

182
Q

Topoisomerase I inhibitors:
MOA
Examples
S/Es

A

Prevent relaxation of supercoiled DNA
Topotecan, irinotecan
Irinotecan causes diarrhoea (I ran to the can)

183
Q

Topoisomerase II inhibitors:
MOA
Examples

A

Prevent recoiling of DNA after transcription
Etoposide, teniposide

184
Q

Topoisomerase I and II inhibitors: S/Es

A

Myelosuppression, mucositis, 2ndary malignancies (AML)

185
Q

Anthracyclines:
MOA

A

Intercalate DNA, inhibit topoisomerase II, generate ROS, perhaps alkylation

186
Q

Anthracyclines:
Examples
S/Es

A

Doxorubicin, daunorubicin, idarubicin, epirubicin
Biventricular HF, necrotic w/ extravasation

187
Q

Monoclonal antibodies: name origins

A

-Omab from mouse
-Ximab chimeric (cross between human/mouse)
-Umab humanised
-Mumab is fully human

188
Q

Monoclonal antibodies: trastuzumab
Target
Treats

A

HER2
Breast cancer

189
Q

Other chemotherapeutic agents:
Bleomycin
Causes
S/Es

A

Lung toxicity
Pulmonary fibrosis, interstitial pneumonitis, hypersensitivity pneumonitis (cough, infiltrates)

190
Q

Other chemotherapeutic agents: hormonal therapies (tamoxifen)
MOA

A

Antioestrogens block oestrogen stimulation of breast cancer

191
Q

Other chemotherapeutic agents: aromatase inhibitors (anastrozole, letrozole)
MOA

A

Block synthesis of oestrogen

192
Q

Other chemotherapeutic agents: antiandrogens
MOA

A

Block androgen stimulation of prostate cancer

Pharmacy 301 (23 decks)

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