Vicki Past Paper Questions Flashcards
What are the causes, symptoms, signs and management of neutropenic sepsis? [9]
- Neutropenia: low neutrophil levels, specifically, <1.5x10^9/L and can be caused by chemo, radiotherapy or a disease with bone marrow involvement.
- As neutrophils make up the majority of WBCs, patients are at increased risk of serious infection, which can cause neutropenic sepsis.
- Risk factors: neuts <0.5x10^9/L, neutropenia >7 days, patients with mucositis (because the lining of the mouth is destroyed), concurrent illness, poor performance status.
- Clinical presentation: pyrexia, treat as NS if two readings above 38C or one above 39C.
Others: diarrhoea, deterioration in general condition. - Common sites of infections: GI tract, respiratory tract and skin. Viral, fungal or bacterial. Gram-ve. Fungal: candida, aspegillus.
- Start treatment with empirical antibiotics straight away: IV broad spectrum antibiotics: tazocin (anti-pseudomonal) and aminoglycoside (gentamacin), in order to cover most common and virulent organisms.
- Add in metronidazole if colonic or dental involvement for anaerobic cover.
- If patient is still pyrexial after 48 hours, change antibiotics to vanco and ceftazidine. If still after 96 hrs add amphotercin B.
- Investigations to perform:
blood cultures, MSU, swabs etc.
Why is neutropenic sepsis serious?
- Neutropenia: low neutrophil levels, specifically, <1.5x10^9/L and can be caused by chemo, radiotherapy or a disease with bone marrow involvement.
- As neutrophils make up the majority of WBCs, patients are at increased risk of serious infection, which can cause neutropenic sepsis.
- Risk factors: neuts <0.5x10^9/L, neutropenia >7 days, patients with mucositis (because the lining of the mouth is destroyed), concurrent illness, poor performance status.
How does Neutropenic sepsis present?
- Clinical presentation: pyrexia, treat as NS if two readings above 38C or one above 39C.
Others: diarrhoea, deterioration in general condition. - Common sites of infections: GI tract, respiratory tract and skin. Viral, fungal or bacterial. Gram-ve. Fungal: candida, aspegillus.
What are the common sites of infection in Neutropenic sepsis?
- Common sites of infections: GI tract, respiratory tract and skin. Viral, fungal or bacterial. Gram-ve. Fungal: candida, aspegillus.
How is neutropenic sepsis managed?
- Start treatment with empirical antibiotics straight away: IV broad spectrum antibiotics: tazocin (anti-pseudomonal) and aminoglycoside (gentamacin), in order to cover most common and virulent organisms.
- Add in metronidazole if colonic or dental involvement for anaerobic cover.
- If patient is still pyrexial after 48 hours, change antibiotics to vanco and ceftazidine. If still after 96 hrs add amphotercin B.
- Investigations to perform:
blood cultures, MSU, swabs etc.
Which medicines are often used as prophylaxis in neutropenic patients and what is the rationale for using each of these medicines?
- Antibiotics e.g. ciprofloxacin (broad spec antibiotic that provides good gram negative cover) as most infections are bacterial. Gram negative infections are often more difficult to treat so it is important that the prophylactic antibiotic covers gram negative infections.
- Antifungal e.g. nystatin, fluconazole as fungal infections have a high mortality rate
- Mouth care using chlorhexidine mouth wash, as mouth is a common entry site of organisms.
- There purpose is to prevent the development of potentially severe infections or sepsis during the neutropenic phase
- Prophylaxis is only continued for the high risk period, once neutrophils go >1 discontinue
How long is NS prophylaxis continued for?
- Antibiotics e.g. ciprofloxacin (broad spec antibiotic that provides good gram negative cover) as most infections are bacterial. Gram negative infections are often more difficult to treat so it is important that the prophylactic antibiotic covers gram negative infections.
- Antifungal e.g. nystatin, fluconazole as fungal infections have a high mortality rate
- Mouth care using chlorhexidine mouth wash, as mouth is a common entry site of organisms.
- There purpose is to prevent the development of potentially severe infections or sepsis during the neutropenic phase
- Prophylaxis is only continued for the high risk period, once neutrophils go >1 discontinue
What is the role of growth factors in neutropenia?
- Granulocyte-colony stimulating factor (G-CSF) e.g. lenograstim may shorter the period of neutropenia after chemotherapy and therefore reduce the risk of infection.
- Not routinely given because of the cost, reserved for patients on chemotherapy regimens where we know there is a high risk of neutropenia or if patient has previously had an episode of sepsis then we usually give to them for the remainder of their cycles.
- Can prevent delays in treatment, consider if dose reduction may compromise outcome. Consider for patients who have potentially curable disease, and for whom delays in their treatment could reduce of cure.
For Iplimumab: describe its mechanism of action, its side effects and its place in therapy [4]
- Metastatic melanoma: NICE approved for previously untreated advanced stage 4 melanoma or after previous therapy.
- Recomb human monoclonal antibody.
- Binds to CTLA-4, the immune checkpoint that downregulates T cell activation and prevents autoimmunity. Thus allows Iplimumab to potentiate an antitumour response.
- Side effects: due to increase immune response so diarrhoea, rash, priritus, N and V, decreased apetite, abdominal pain, hepatitis.
What are the Ipilimumab side effects other than the usual of nausea, vomiting, diarhoea? [4]
Decreased appetite
Pruritits
Abdominal pain (normal for this type of treatment?)
Hepatitis
For Vemurafenib, describe its mechanism of action, its side effects and its place in therapy [3]
- Vemurafinab is an oral tyrosine kinase BRAF inhibitor: B-raf 600, normal valine at pos 600 is replaced with glutamic acid causing constitutive activity in 60% MM patients.
2. Side effects: Fatigue Joint pain (painkillers, icepacks) Alopecia Pruritus (antihistamines, emollients) Headache, Sensitivity to sun (SPF 30-50 needed etc.)
- Important side effects: cutaneous squamous cell carcinomas in 20% pts (dab: 10% but eye problems)
For Bevacizumab: describe its mechanism of action, its side effects and its place in therapy [3]
- Avastin, anti-VEGF monoclonal antibody blocks VEGFR activation preventing angiogenesis needed for tumour growth but does not get rid of existing blood vessels.
- IV infusion every 2/3 weeks in combination with 5-FU/Capectabine based chemo in Metastatic colorectal cancer.
- Serious side effects:
Gi perforation, hemorrhage, hypertension (34%), arterial thromboembolism.
For Trastuzumab:
describe its mechanism of action, its side effects and its place in therapy [3]
- Herceptin, antibody for extracellular portion of HER2 receptor. Used in HER2 positive patients if overexpression is >3.
` - NICE approved for metastatic BC, given as long as disease responds and for early BC.
- Side effects of cardiotoxicity (HER2 in heart), NV, diarrhoea, myalgia/arthralgia, rash.
What is the rationale behind using hormonal therapies in breast cancer?
Give some examples of drugs that are commonly used and their side effects.
Hormonal therapies – aim is to reduce the oestrogen/progesterone levels as this is driving cell growth.
Tamoxifen – ostrogen antagonist, acts on oestrogen receptors on cells. Oestrogen can still bind the DNA, but adapts a confirmation that prevents the recruitment of cofactors. Generally well tolerated but side effects tend to mimic symptoms of the menopause, including hot flushes, weight gain. There is an increased risk of developing endometrial cancer. Tamoxifen is the main hormonal therapy that is given to women who HAVENT been through the menopause.
Aromatse inhibitors – anostrazole
- Blocks the conversion of androgens from adrenal cortex to oestrogens in peripheral tissues
- Only effective in post menopausal women
- One of the key side effects in decreased bone mineral density, therefore all patients must have a bone density scan when treatment is started (DEXA scan)
What is the rationale behind using hormonal therapies in prostate cancer?
Describe how luteinizing hormone–releasing hormone (LHRH) analogues e.g. goserelin, work in this disease and how androgen blockers e.g. bicalutamide, work.
• Hormonal therapies block androgen drive that sustains most prostate cancers i.e. testosterone.
• LHRH analogues
- Disrupt the normal pulsatile release of LHRH
- Initially increases LH, once receptors are desensitized then get decreased LH and testosterone levels
- The initial increase in LH can cause a transient increase in tumor volume (tumor flare) which can worsen symptoms if not blocked
- Therefore, need to get an androgen blocking drug
• Androgen blocking drugs compete with DHT (dihydrotesterone) which is the active testosterone metabolite, at a receptor level within prostate cancer cells.
• Side effects are due to decreased testosterone levels – impotence, loss libido, gynacemostia, breast tenderness, hot flushes, depression and mood changes, fatigue
At what stage might abiraterone be used in prostate cancer and how does it work?
- Abiraterone is licensed for metastatic prostate cancer where chemotherapy is not yet clinically indicated
- Also licensed after failure of hormone therapy
- Inhibits androgen production from testes, adrenal gland and prosate tumor cells
List 8 risk factors that may increase a woman’s chance of developing Breast Cancer:
- Geographical location
- COC – if taken for 4 years below the age of 25
- Pregnancy later in life
- Not breastfeeding (deplete mammary stem cells)
- HRT – risk during and for 5 years after
- Early onset of periods (age of menarche)
- Diet, overweight
- Genetic – BRAC1/2 genes
- Age – main risk factor breast cancer, risk doubles every 10 years until menopause where risk slows
- Previous benign breast disease
What factors influence Breast Cancer prognosis? [4]
- HER2+ breast cancers are associated with a more aggressive phenotype, cancers will progress quicker and more likely to metastasize.
- ER/PG negative:
Measure the concentration of receptors as this will predict the patients response to hormonal therapies such as tamoxifen and anastrozole. Therefore, if negative, worse prognosis as less treatment options. - TNM staging:
-early breast cancer (T1, N0, M0) has 85% year survival rate
Metastatic breast cancer <5% 15 year survival
Increased TNM stage
Poorly differentiated tumours are more likely to grow and spread faster. - Diagnosis at a younger age is associated with a worse prognosis – women aged <34 years, less than 50% will survive 5 years and most will relapse in 3 years.
Eribulin is a new chemotherapy agent used in advanced breast cancer. Describe its mechanism of action.
Eribulin is a mechanistically unique inhibitor of microtubule dynamics,[9][10] binding predominantly to a small number of high affinity sites at the plus ends of existing microtubules.[11][12] Eribulin exerts its anticancer effects by triggering apoptosis of cancer cells following prolonged and irreversible mitotic blockade.[13][14]
