Chapter 2- Vicki Flashcards
1
Q
Give 8 things to check for breast cancer
A
1) changes in texture (puckering/dimpling)
2) feel lumps and thickening
3) nipple discharge
4) nipple inversion/direction
5) swelling in armpit/collar bone
6) change in size/shape
7) constant pain in armpit/breast
8) rash/crusting or nipple
2
Q
Name 4 diagnostic tests for breast cancer
A
1) examination of symptoms
2) mammography (low level x-ray)
3) breast ultrasound
4) fine needle aspirate/biopsy
3
Q
What gives a worse breast cancer prognosis?
A
1) higher TNM stage
2) poorly differentiated
3) lymph or vascular invasion (metastatic)
4) ER or PR -ve
5) HER2+
6) Young diagnosis (<34yrs)
4
Q
List the 6 categories of treatments for breast cancer
A
Surgery Radiotherapy Chemotherapy Hormonal therapies Monoclonal antibodies New agents
5
Q
What’s the rationale for using hormonal therapies to treat breast cancer?
A
Sensitive cancer cells need oestrogen to stay alive therefore by removing oestrogen is very effective at controlling or killing hormone-sensitive cancer cells
6
Q
Name four hormonal therapies used in the treatment of breast cancer
A
Tamoxifen
Anastrozole
Letrozole
Exemestane
7
Q
Name the types of drug that come under the class known as aromatase inhibitors and describe how they work
A
Anastrozole
Letrozole
Exemestane
Blocks the conversion of androgens from adrenal cortex
8
Q
List the side effects of anastrozole
A
Decrease bone density Arthritis Diarrhoea Anorexia Bone pain
9
Q
What’s the hormonal drug of choice in postmenopausal women with ER/PR+be breast cancer
A
Anastrozole
10
Q
Name three drugs used in the FEV100 chemotherapy regimen for breast cancer
A
Fluorouracil
Epirubicin
Cyclophosphamide
11
Q
What drug in the FEV100 chemo regimen is responsible for the cardiac problems?
A
Epirubicin
12
Q
Name a monoclonal antibody used in the treatment of HER2+ breast cancer
A
trastuzumab (herceptin)
13
Q
How does trastuzumab work?
A
Recombinant humanised monoclonal antibody- binds HER2 prevents binding of EGF and also involved in antibody-dependent cell-mediated cytotoxicity
14
Q
Name 5 side effects of trastuzumab
A
Cardiotoxicity Nausea and vomiting Diarrhoea Myalgia/arthralgia Rash
15
Q
What is everolimus?
A
Selective mammalian target of rapamycin inhibitor (mTOR)
-mTOR is a key serine-threonine kinase which is upregulated in breast cancer
16
Q
What is everolimus licensed for?
A
Oral agent licensed for treatment of ER/PR +ve, HER2-ve advanced metastatic breast cancer, in combination with exemestane in postmenopausal women after progression following hormonal treatment
17
Q
Side effect of everolimus
A
Stomatitis Rash Fatigue Diarrhoea Infections Nausea Decreased appetite
18
Q
Name a new monoclonal antibody licensed in breast cancer and explain its mechanism of action
A
Pertuzumab: recombinant humanised antibody that specifically targets the extracellular dimerisation domain (subdomain 2) of the HER2 thereby blocking ligand-dependent heterodimerisation of HER2. It inhibits ligand-initiated intracellular signalling through MAP/PI3K therefore inhibiting cell growth and causing apoptosis
19
Q
What is pertuzumab licensed for?
A
Neoadjuvant treatment of early breast cancer and in metastatic disease
20
Q
Side effects of pertuzumab
A
Anaemia Arthralgia Chills Constipation Cough Decreased appetite Dry skin
21
Q
List 6 risk factors for lung cancer
A
Smoking Passive smoking Asbestos exposure Radon gas exposure Previous lung disease Family history
22
Q
Non small cell carcinoma can be divided into 3 types what are these?
A
Adenocarcinoma
Squamous cell carcinoma
Large cell carcinoma
23
Q
List 6 symptoms of lung cancer
A
Persistent chronic cough SoB/wheezing Haemoptysis Chest/shoulder/back pain Weight loss Fatigue
24
Q
How can you diagnose lung cancer
A
Symptoms Chest X-ray Bronchoscopy & biopsy Sputum cytology CT scan Lung function tests
25
Name two stages of SCLC
Limited stage disease
| Extensive stage disease
26
What's the treatment of limited stage small cell lung cancer
1st line 4-6 cycles of cisplatin/carboplatin-based chemo + concurrent use of radiotherapy in patients with good performance status
27
What's the treatment of extensive small cell lung disease
Platinum based chemo
28
Treatment of advanced/metastatic NSCLC depends on what things
1) specific tumour histological subtype (adenocarinoma/squamous cell)
2) biomarkers/mutations (EGFR/ALK gene translocation
29
What is crizotinib and when would it be used
It's a small molecule ALK receptor inhibitor used to treat advanced/metastatic NSCLC that's an adenocarcinoma with ALK translocation
30
How would you treat adenocarcinoma NSCLC with no EGFR/ALK mutations?
Cisplatin/pemetrexed chemotherapy
31
What should the urine output be during and for 6-8 hours post cisplatin chemo?
>100ml/hour
32
What fluids should be prescribed for someone on cisplatin
Pre and post hydration- 3L IV fluids before and after
33
Before giving cisplatin what should the GFR be?
>55ml/min
34
You must monitor patient for cisplatin induced wasting of electrolytes - what supplements may be needed?
Mg
Ca
k
35
Pemetrexed is an antifolate agent- to minimise toxity what should be given
Vitamin B12
| Folic acid
36
To reduce skin reactions of from pemetrexed - what is given?
Dexamethasone steroid for 3 days before chemo
37
What is pembrolizumab and how does it work
Humanised monoclonal antibody that acts to block the 'programmed-death 1' protein in order to promote an anti-tumour immune response
38
What is PD-1 and what monoclonal antibody acts to block it
Programmed cell death 1 protein --> part f immune check point pathway (pembrolizumab)
39
Name three drugs you could use in squamous cell carcinoma with EGFR mutation (lung cancer)
Gefitinib (iressa)
Erlotinib (tarceva)
Afatinib
40
Name the two types of non-melanoma skin cancers
Basal cell carcinoma (BCC)
| Squamous cell carcinoma (SCC)
41
What does the letters in the ABCDEF identification of melanoma stand for?
```
A= asymmetrical
B= border
C= colour
D= diameter
E= evolution/elevation
F= funny mole
```
42
List four risk factors for melanoma
Sun exposure (intermittent)
Number of moles
Skin type
Family history
43
How is melanoma diagnosed
1) physical examination
2) dermascope
3) excisional biopsy
4) histopathology
44
Name 4 biological therapies used to treat stage 4 advanced melanoma
Ipilimumab
Pembrolizumab
Vemurafenib
Dabrafenib
45
Name the chemotherapy used the treat stage 4 advanced melanoma
Dacarbazine (alkylating agent)
46
What is ipilimumab
Recombinant human monoclonal antibody that binds to CTLA-4 immune checkpoint blocking the Ligand CD80 and CD86 from binding therefore potentiating the antitumour T-cell response
47
Name a CTLA-4 blocker used in he treatment of sage 4 melanoma
Ipilimumab
48
What is ipilimumab NICE approved for
Previously untreated advanced malignant melanoma or after prior therapy
49
List side effects of ipilimumab
```
Diarrhoea
Rash
Pruritus
Fatigue
Nausea and vomiting
Decreased appetite
Abdominal pain
Colitis, hepatitis
```
50
Down side of ipilimumab
Costs £25,000 for 1 dose (given every 3weeks for 4 doses in total)
51
What is vemurafenib
Is an oral tyrosine kinase inhibitor of BRAF (BRAF is constitutively active in melanoma as a result of a point mutation from glutamic acid to valine at aa 600)
52
Name a BRAF inhibitor
Vemurafenib
53
List side effects of vemurafenib
```
Fatigue
Joint paint
Rash
Sensitive to sun
Nausea
Alopecia
Pruritus
Headache
```
54
Which tyrosine kinase inhibitor has been reported to cause cutaneous squamous cell carcinomas and should be stopped if blistering of the skin occurs
Vemurafenib
55
Name two BRAF inhibitors used in malignant melanoma with BRAF V600 mutation
Vemurafenib
| Dabrafenib
56
What is dabrafenib
BRAF inhibitor
57
List side effects of dabrafenib
```
Fever
Rash
Headache
Nausea
Joint pain
Diarrhoea
Fatigue
```
58
What two serious effects can dabrafenib cause
1) cutaneous squamous cell carcinomas
| 2) uveitis (can damage vision)
59
What is pembrolizumab indicated for
Previously untreated advanced malignant melanoma or following ipilimumab/BRAF inhibitor
60
Which of the two BRAF inhibitors used in malignant melanoma should be taken preferably with food?
Vemurafenib
61
Which of the two BRAF inhibitors used in malignant melanoma should be taken on an empty stomach
Dabrafenib
62
List five risk factors for developing prostate cancer
```
Age
Race
Genetic
Androgens
Diet high in fat & red meat
```
63
List two protective factors against prostate cancer
Frequent ejaculation
| Diet high in lyocpenes (tomatoes)
64
Where is the prostate gland and what does it do
Lies below bladder neck (anterior to rectum, traversed by urethra) it produces the fluid part of semen
65
What type of cancer is cancer of the prostate and where does it commonly metastasise to
Adenocarcinoma
| Bones
66
What are prostate cancer symptoms similar to
Benign prostatic hyperplasia
67
List 6 clinical presentations of prostate cancer
```
Hesitancy
Post-micturition dribbling
Reduced void pressure
Frequency
Urgency
Nocturia
```
68
List 4 extra symptoms of locally invasive prostate cancer
Perineal pain
Impotence
Incontinence
Haematospermia
69
List 6 symptoms of metastatic prostate cancer
```
Bone pain
Hypercalcaemia
Spinal cord compression
Sciatica/paraplegia
Fracture
Lymphoedema
```
70
In prostate cancer: locally invasive symptoms result from what?
Invasion of neural structures, bladder base and perirectal tissues
71
Name five diagnostic techniques used for prostate cancer
```
Digital rectal examination
Prostate specific antigen
Transurethral ultrasound
CT/MRI scan
Radiolabelled bone scanning
```
72
What's the problem with a digital rectal examination in prostate cancer
It cannot detect T1 disease
73
In prostate cancer, are increased levels of PSA completely diagnostic?
No:
20% won't have raised levels
PSA can be raised for other reasons (age, BPH)
74
List 6 treatment options in prostate cancer
```
Watchful waiting
Surgery (radical prostatectomy)
Radiotherapy
Brachytherapy
Hormonal therapy
Chemotherapy
```
75
What are the side effects of radical prostatectomy surgery and when is it performed
Impotence and incontinence, performed in a potentially curative setting
76
When is radiotherapy indicated in prostate cancer
Patients who are not suitable for surgery but have good life expectancy and localised disease. Also used for symptoms control in advanced disease and bony metastasis
77
What is brachytherapy, what cancer is it used in
It delivers radiation through implantation of needles containing radioactive pellets into the prostate gland (prostate cancer)
78
How long are brachytherapy pellets left in the prostate gland for?
Permanently and they emit low levels of radiation over several weeks/months
79
How is brachytherapy carried out?
Under general/spinal anaesthesia
80
What's the rationale for hormonal therapies in prostate cancer
Hormone therapies block the androgen drive that sustains most prostate cancers
81
Testosterone and other androgens are metabolised to what active metabolite
Dihydrotestosterone (DHT)
82
Where are androgens produced
Testosterone- tests
| 10% of androgens produced by adrenal gland
83
What's the pathway to testosterone release
hypothalamus--> luteinizing hormone releasing hormone --> pituitary gland --> luteinizing hormone --> testes --> testosterone
84
Why is LHRH released from the hypothalamus in a pulsatile manner?
Pulsatile release is important as receptors for LHRH will become desensitised if they are permanently occupied
85
Name five ways to achieve androgen blockade in prostate cancer
1) bilateral orchidectomy
2) LHRH analogues
3) androgen blockers
4) LHRH analogues + androgen blockers
5) intermittent hormonal therapy
86
In prostate cancer how does bilateral orchidectomy work
Hormonal therapy used to stop testicular secretion of testosterone
87
What's the rationale for using LHRH analogues in prostate cancer
Disrupt normal pulsatile release of LHRH causing desensitisation of receptors eventually resulting in a decrease in LH and testosterone (after initial increase release tumour flare)
88
Name two LHRH analogues used as hormonal therapies in prostate cancer
Goserelin
| Triptorelin
89
What should be used for the first few weeks of using LHRH analogues in prostate cancer and why
Androgen blocking drug- bicalutamide/cyproterone due to initial increase in LH and testosterone (tumour flare)
90
Name two androgen blockers
Bicalutamide
| Cyproterone
91
What's the MOA of bicalutamide and cyproterone
Block the active metabolite of androgens (dihydrotestosterone) at the receptor level within prostate cells
92
List side effects of using hormonal therapies in prostate cancer and why do they occur?
```
Impotence
Loss of libido
Gynaecomastia
Breast tenderness
Hot flushes
Depression/mood changes
Fatigue
--> due to reduced testosterone
```
93
Name a new therapy for metastatic prostate cancer
Abiraterone
94
How does abiraterone work
Used in metastatic prostate cancer- irreversible inhibitor of CYP17A1 (enzyme responsible for androgen and cortisol production)
95
What must abiraterone be given with?
Steroid (prednisone)
96
Abiraterone inhibits the production of androgens from where?
3 sources:
Testes
Adrenal gland
Prostate tumour cells
97
What is enzalutamide
New therapy used in prostate cancer: is a potent androgen receptor signalling inhibitor that blocks several steps in the androgen receptor signalling pathway
98
How does enzalutamide work
1) inhibits binding of androgens to androgen receptors
2) inhibits nuclear translocation of activated receptors
3) inhibits the associated of the activated androgen receptor with DNA
99
List the side effects of enzalutamide
```
Headache
Hot flushes
Memory problems
Visual hallucinations
Risk of seizures
```
100
Name two new therapies used in metastatic prostate cancer
Abiraterone
| Enzalutamide
101
When is abiraterone and enzalutamide indicated?
In metastatic prostate cancer that's not yet requiring chemo or in failure of hormonal/chemotherapy
102
Commonly used Chemo regimen in prostate cancer
Docetaxel and prednisolone
103
Why do patients not like docetaxel
Many side effects and given IV
104
Why is prednisolone given alongside docetaxel
We think docetaxel inhibits androgen from adrenal glands (combination used in prostate cancer)
105
When is the chemo regimen docetaxel and prednisolone indicated in prostate cancer
Hormone refractory metastatic prostate cancer
106
List side effects of the docetaxel prednisolone regimen used in prostate cancer
```
Bone marrow suppression
Severe alopecia
Nausea and vomiting
Myalgia/arthralgia
Fluid retention
Hypersensitivity
```
107
What do you give before the docetaxel and prednisolone regimen in prostate cancer
Dexamethasone
108
What type of chemo is most effective in breast cancer
Anthracycline based chemo
109
what is DD3PCA3
New prostate specific - way of monitoring better than PSA
110
What is molecular and functional imagining (MFI)?
Molecular shows receptor/gene expression, functional shows aspects of angiogenesis and metabolism - way of imaging
111
Micro arrays allow the measurement of what?
Gene expression levels
112
Two main applications of using microarrays in cancer
1) Determination of expression levels of genes
| 2) Identification of sequence (gene mutation)
113
Microarray technology utilises what?
The fact that mRNA is designed as a complementary sequence to the DNA it was copied from
114
Colorectal cancer is more common in females
False MALES
115
What is FAP
Familial adenomatous polyposis -> autosomally dominant inherited condition (colorectal cancer)
116
What is HNPCC
Hereditary non-polyposis colorectal cancer accounts for higher hereditary colorectal cancer than FAP
117
Pathology of colorectal cancer
Polyp--> benign adenocarcinoma --> malignant tumour
118
List the risk factors for colorectal cancer
```
Familial (FAP/HNPCC)
Animal fat/red meat
Low fibre
Inactive
Obesity
Smoking
Previous colorectal cancer
Crohns and colitis
Male
Age
```
119
Signs of colorectal cancer
```
Change in bowel habit
Abdominal pain
Rectal bleeding/mucus
Weight loss
Anorexia
Anaemia due to chronic bleeding from tumour site
```
120
What is FOB and when is it used
Faecal occult blood --> used in the screening for colorectal cancer in everyone aged 60-74 every 2 years
121
Name the two types of surgery in colorectal cancer
Hemicolectomy
| Sigmoid colectomy
122
True or false, colorectal cancers radiation is only used for rectal cancers
True
123
Adjuvant chemo used in colorectal cancer 5-FU .. why do we give folinic acid as well
Increases and prolongs inhibition of thymidylate synthase improving clinical outcome
124
Side effects of 5-FU
```
Diarrhoea
Stomatitis
N&V
Bone marrow suppression
Hand and foot syndrome
Excessive tear shedding
```
125
What is the oxaliplatin de gramont (FOLFOX) regime for what cancer
Oxaliplatin
5-FU
folinic acid
Colorectal cancer
126
Side effects of oxaliplatin
Peripheral neuropathy
Acute pharyngolaryngeal dysasthesia
Bone marrow suppression
Mild alopecia
127
Why is the oxaliplatin de gramont regime an infusion in colorectal cancers
Tumour cells have low growth fraction and 5-FU is S phase specific and has a T1/2 of 10 mins
128
Negative of oxaliplatin de gramont being an infusion?
Increased incidence of hand and foot syndrome
129
What are the issues with infusion devices
Anxiety for patients
Disposal of cytotoxics in home
Time consuming to fill
130
What's in the XELOX regime and what cancer is it used for
Oxaliplatin and capecitabine
131
What is capecitabine and how is it activated
Oral prodrug of 5-FU -> 3 step activation, 2 of which occur in tumour cells
132
4 advantages of oral chemo
Less invasive/distressing
No issues with sterility/expiry
Reduced pharmacy costs and time
Patient can administer themselves
133
Side effects of capecitabine
Diarrhoea
N&v
Hand and foot syndrome
Stomatitis
134
What is irinotecan
Topoisomerase 1 inhibitor (used in metastatic colorectal cancer to prevent unwinding of DNA and therefore preventing DNA replication)
135
What is in Lonsurf and what cancer is it used to treat
Trifluridine-tipiracil
Trifluridine= thymidine analogue (degraded by thymidine phosphorylase TPase)
Tipiracil= TPase inhibitor
Used in metastatic colorectal cancer
136
Side effects of lonsurf (trifluridine-tipiracil)
```
N&V
Diarrhoea/constipation
Source mouth
Taste changes
Bone marrow suppression
Anaemia
Hand and foot syndrome
Alopecia
Tiredness
```
137
Name two monoclonal antibodies used in metastatic colorectal cancer
Bevacizumab
| Cetuximab
138
Name 4 treatment related oncological ermergencies
Neutropenia sepsis
Extravasation
Tumour Lydia syndrome
Thrombocytopenia
139
What are the levels in hypercalcaemia
```
Normal= 2.2-2.7mmol/L
Treat= 2.7-3.7mmol/L
Emergency= > 3.7mmol/L
```
140
Calcium levels >3.7mmol/L can cause what
Cardiac arrhythmias/arrest
141
Hypercalcaemia particularly occurs in what 4 cancers
Lung
Breast
Prostate
Myeloma
142
Treatment of hypercalcaemia
Rehydration
| Bisphosphonates
143
How long do bisphosphonates take to have maximal effect in hypercalcaemia
3-5 days
144
Example of bisphosphonate used to treat hypercalcaemia
Disodium pamidronate IV infusion
145
What is the levels of neutrophils in neutropenia
<1.5 * 10^9/L
146
What can cause neutropenia
Chemo
Radio
Disease with bone marrow
147
Neutropenic sepsis is often caused by part of hosts own gut or skin flora which involve what 4 pathogens
Staphylococcus aureus
Streptococcus
Klebsiella
E.Coli
148
The longer an individual has neutropenia the higher their risk of what type of infection
Fungal (candida or aspergillus)
149
Risk factors for neutropenic sepsis
Neutrophil count <0.5*10^9/L
Neutropenia lasting >7days
Patients with mucositis
150
Treatment of neutropenic sepsis
```
Tazocin + gentamicin
(+metronidazole)
After 48hrs change to:
Ceftazidime + vancomycin
(+ amphotericin B)
```
151
Treatments used for fungal infections in neutropenic sepsis
Fluconazole -candida
Itracobazole -candida, aspergillus
Amphotericin B- best spectrum
152
Prophylaxis of neutropenic sepsis
Ciprofloxacin
Antifungal- nystatin, fluconazole, itraconazole
Mouthcare-chlorhexidine
153
What is lenograstim
Granulocyte colony stimulating factor may shorten the period of neutropenia after chemo
