BNF - Chapter 8 - Immune system and malignant disease Flashcards
Which immunosuppressant drugs have a role in the management of inflammatory bowel disease?
- Azathiopurine
- Ciclosporin
- Mercaptopurine
- Methotrexate
Other than chronic inflammatory diseases when else are immunosuppressants used?
They are used to suppress rejection in organ transplant recipients and to treat a variety of chronic inflammatory and autoimmune diseases.
What may modification of tissue reactions caused by corticosteroids and other immunosuppressants result in?
The rapid spread of infection
What do antiproliferative drugs do?
Antiproliferative agents, also known as antimetabolites, inhibit cell-cycle pathways to limit T- and B-cell proliferation and thereby reducing the cytotoxic response directed toward the cardiac allograft.
Give a list of some antiproliferative immunosuppressants?
- Azathioprine
-Mercaptopurine - ## Mycophenolate mofetil
What is azathioprine metabolised to?
Mercaptopurine
When azathioprine is given with allopurinol should the dose stay the same?
Doses should be reduced when allopurinol is given concurrently
Which has a more selective mode of action - mycophenolate or azathioprine?
Mycophenolate
Are the corticosteroids immunosuppressants?
Yes they are powerful immunosuppressants
They are used to prevent organ transplant rejection, and in high dose to treat rejection episodes
What inhibitor is ciclosporin?
Calcineurin inhibitor
Is ciclosporin an immunosuppressant?
Yes - it is a potent immunosuppressant which is virtually non-myelotoxic but markedly nephrotoxic
Name another calcineurin inhibitor?
Tacrolimus;
Although not chemically related to ciclosporin it has a similar mode of action and side effects
Is the incidence of neurotoxicity greater with ciclosporin or tacrolimus?
It is greater with tacrolimus than with ciclosporin
Name a non-calcineurin inhibiting immunosuppressant licensed for renal transplantation?
Sirolimus
What is myelosuppression?
Suppression of the immune system
Azathioprine is an immunosuppressant metabolised to?
Mercaptopurine
What are some hypersensitivity reactions of azathioprine?
- malaise
- dizziness
- Vomiting
- Diarrhoea
- Fever
- Myalgia
- rash
- hypotension
- renal dysfunction
What should patients do if they experience any of these hypersensitivity reactions?
Withdraw treatment immediately
What blood disorders can azathioprine cause?
Neutropenia and thrombocytopenia
Neutropenia is dose-dependent
What does the management of neutropenia and thrombocytopenia induced by azathioprine require?
Careful monitoring and dose adjustment
What symptom is common in the early stages of treatment with azathioprine?
- Nausea is common and usually resolves in a few weeks without changing the dose.
With azathioprine how can moderate nausea be managed?
By using divided daily doses, taking doses after food, prescribing antiemetics or temporarily reducing the dose
What pre-screening treatment is important with azathioprine?
The enzyme thiopurine methyltransferase (TPMT) which metabolises thiopurine drugs (azathioprine, mercaptopurine, etc.)
What risk is increased in patients with reduced activity of the enzyme TPMT?
Increases the risk of myelosuppression in patients with reduced activity of this enzyme (TPMT), thus TPMT activity should be measured before starting treatment
Which patients should not receive azathioprine based on their TPMT levels during pre screening?
Patient with absent TPMT activity should not receive this drug, those with reduced TPMT activity may be treated under specialist supervision
what monitoring requirements are there for azathioprine?
Monitor for toxicity throughout the treatment
Monitor full blood count weekly (more frequently with higher doses or if severe hepatic or renal impairment) for the first 4 weeks…. thereafter reduce the frequency of monitoring to every 3 months
• Blood tests and monitoring for myelosuppression are essential in long-term treatment.
Is azathioprine prescribing brand specific?
Yes it is so it should be prescribed by brand
Ciclosporin is a potent immunosuppressant - does it also cause myelosuppression?
Not but it is nephrotoxic (toxic to the kidneys)
Does same brand need to be maintained for ciclosporin?
Yes - patients should be stabilised on a particular brand because switching between formulations without close monitoring can lead to important changes in blood-ciclosporin concentrations
What are the common side effects when ciclosporin is used as an eye drop?
common side effects include eye discomfort and inflammation… as well as blurred vision.
What are the monitoring requirements of ciclosporin?
- blood ciclosporin concentration should be monitored throughout treatment
- Renal function should be monitored - an increase in serum creatinine and urea may call for a dose reduction (in transplant patients) or discontinuation of treatment (in non-transplant patients)
- Blood pressure should be monitored - discontinue if hypertension develops that cannot be controlled with antihypertensive
Blood lipids should be measured before and after the first month of treatment - Monitor liver function
Before starting ciclosporin treatment for psoriasis and eczema how many times should blood pressure and renal function be measured?
Atleast twice
In rheumatoid arthritis - for ciclosporin what other parameter would be monitored?
- Serum creatinine at least twice before treatment.
During treatment, monitor serum creatinine every 2 weeks for the first 3 months and then every month for a further 3 months.
Patients on ciclosporin should be advised to avoid what?
Avoid excessive exposure to UV light, including sunlight.
Is tacrolimus calcineurin inhibitor?
Yes which acts to suppress the immune system
Switching between oral tacrolimus products have been associated with what?
Associated with toxicity and transplant rejection
Do oral tacrolimus need to be prescribed by brand?
YEs to maintain therapeutic response
Give the different brands of tacrolimus and their daily frequency of administration?
daily (once in the morning and once in the evening)
- Modigraf granules make an immediate release oral suspension which is taken TWICE daily (once in the morning and once in the evening)
- Advagraf is a prolonged-release capsule that is taken ONCE daily in the morning.
What has been reported with tacrolimus blood concentrations much higher than the maximum levels in children?
Cardiomyopathy (disease of the heart muscle) has been reported to occur primarily in children with tacrolimus blood trough concentrations much higher than the recommended maximum levels.
For cardiomyopathy risk with tacrolimus what should patients be monitored for?
Patients should be monitored by echocardiography for hypertrophic changes – consider dose reduction or discontinuation if these occur.
Is mycophenolate mofetil a immunosuppressant?
Yes
With mycophenolate what should be measured if there is recurrent infection?
Measure serum immunoglobulin and consider bronchiectasis (abnormal widening of the bronchi causing infection) or pulmonary fibrosis if persistent respiratory symptoms such as cough and dyspnoea (difficulty breathing) develop.
What other counselling should be given to patients taking mycophenolate mofetil?
- patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. infection or unexplained bruising or bleeding.
What should be excluded before starting mycophenolate?
- exclude pregnancy in females of child bearing age
- 2 pregnancy tests 8-10 days apart are recommended
- women should use at least 1 form of effective contraception before and during treatment, and for 6 weeks after discontinuation - 2 methods of effective contraception are preferred.
What is multiple sclerosis?
Multiple sclerosis is a chronic, immune-mediated, demyelinating inflammatory condition of the central nervous system, which affects the brain, optic nerves and spinal cord, and leads to progressive severe disability.
What is the pattern of the disease?
Relapsing-remitting multiple sclerosis is the most common pattern of the disease. It is characterised by periods of exacerbation of symptoms (relapses) followed by unpredictable periods of stability (remission).
On average how times a year does it occur?
The severity and frequency of relapses varies greatly between patients, but on average occur once or twice per year.
What does the clinical pattern of multiple sclerosis lead to?
This clinical pattern often develops into secondary-progressive multiple sclerosis, with progressive disability unrelated to relapses.
Most patients develop secondary progressive disease 6–10 years after onset.
What is active disease (multiple sclerosis) defined as?
as at least two clinically significant relapses occurring within the last 2 years.
What is highly active disease characterised as?
by an unchanged/increased relapse rate or by ongoing severe relapses compared with the previous year, despite treatment with interferon beta
What is rapidly-evolving severe relapsing-remitting multiple sclerosis defined as?
By two or more disabling relapses in 1 year and one or more gadolinium-enhancing lesions on brain magnetic resonance imaging (MRI) or a significant increase in T2 lesion load compared with a previous MRI.
Is there a cure for multiple sclerosis?
No there is no cure for this
Which drugs are used in the treatment of multiple sclerosis in England?
- Interferon beta
- Glatiramer Acetate
- Fingolimod
- Natalizumab
What is believed to be a risk factor for developing multiple sclerosis?
Low levels of vitamin D
What are patients with diagnosed multiple sclerosis usually given?
Regular vitamin D after assessment of their serum levels of vitamin D, but there is insufficient evidence to support its use as a treatment for multiple sclerosis.
Patients should not be offered vitamin D solely for the purpose of treating multiple sclerosis.
What is recommended for active relapsing-remitting multiple sclerosis?
. Interferon beta and glatiramer acetate
- Peginterferon beta-1a requires less frequent administration and is available as an alternative to the non-pegylated interferon beta therapies.
Which drugs are preferred options for active disease?
Teriflunomide and dimethyl fumarate are treatment options for patients with active disease. They may be preferred due to their oral route of administration.
More active disease may be treated with what?
with natalizumab or alemtuzumab.
Which is the only one recommended for the treatment of rapidly-evolving severe relapsing-remitting multiple sclerosis?
natalizumab
Which is the only drug licensed to be used in secondary progressive multiple sclerosis?
- Interferon beta 1b
Is there any drugs available for primary progressive multiple sclerosis?
Currently there are no effective disease-modifying treatments licensed for primary progressive multiple sclerosis
Are there any specific treatment for progressive-relapsing multiple sclerosis?
No specific treatment options for this type of multiple sclerosis. None of the currently licensed disease-modifying drugs are recommended in non-relapsing progressive disease.
Other than neurological dysfunction of multiple sclerosis - what are some of the other chronic symptoms?
- chronic symptoms (such as fatigue, spasticity, visual problems, and emotional lability) produce much of the disability in multiple sclerosis.
What can increase the progression of disability in multiple sclerosis?
Smoking - therefore smoking cessation should be encouraged
For suspected relapses what is recommended first line?
Oral methylprednisolone is recommended as the first-line option. Intravenous methylprednisolone should be considered as an alternative if oral methylprednisolone has failed or is not tolerated or if hospitalisation is required.
Are vitamin B12 injections recommended as treatment for fatigue in patients with multiple sclerosis?
No
Which drug is licensed for the improvement of walking in patients with multiple sclerosis?
- Fampridine
NICE do not consider it to be a cost-effective treatment and do not recommend its use.
What factors may aggravate spasticity in multiple sclerosis?
constipation, infection, poor mobility aids, pressure ulcers, posture and pain
What are the first line options of managing spasticity in multiple sclerosis?
- Baclofen
or - Gabapentin (unlicensed)
What are second and third line options for spasticity in multiple sclerosis?
Tizanidine or dantrolene sodium are second-line options; benzodiazepines may be used as third-line therapy and may also be effective in treating nocturnal spasms.
If other treatments are not effective then a 4 week trial of what can be offered?
A 4-week trial of cannabis extract can be offered as adjunctive treatment for moderate to severe spasticity in multiple sclerosis if other pharmacological treatments are not effective.
Is interferon beta a biological medicine?
Yes
What should be noted about prescribing biological medicines?
Biological medicines must be dispensed by brand name
Manufacturer advises to record the brand name and batch number after each administration
What do cytotoxic drugs have?
They have both anti-cancer activity and the potential to damage normal tissue
Are most cytotoxic drug teratogenic?
Yes
What are the pros and cons of combination of cytotoxic drugs?
Combinations of cytotoxic drugs, as continuous or pulsed cycles of treatment, are frequently more toxic than single drugs but have the advantage in certain tumours of enhanced response, reduced development of drug resistance and increased survival. However for some tumours, single-agent chemotherapy remains the treatment of choice.
What are the key points of cytotoxic drug handling guidelines?
Trained personnel should reconstitute cytotoxics
Reconstitution should be carried out in designated pharmacy areas
Protective clothing (including gloves, gowns, and masks) should be worn
The eyes should be protected and means of first aid should be specified
Pregnant staff should avoid exposure to cytotoxic drugs (all females of child-bearing age should be informed of the reproductive hazard)
Use local procedures for dealing with spillages and safe disposal of waste material, including syringes, containers, and absorbent material
Staff exposure to cytotoxic drugs should be monitored
What is the dosing of cytotoxic drugs determined by?
using a variety of different methods including body-surface area or body-weight. Alternatively, doses may be fixed.
Doses may be further adjusted following consideration of a patient’s neutrophil count, renal and hepatic function, and history of previous adverse effects to the cytotoxic drug. Doses may also differ depending on whether a drug is used alone or in combination.
what is oral mucositis - from chemotherapy?
A sore mouth is a common complication of cancer chemotherapy; it is most often associated with fluorouracil, methotrexate, and the anthracyclines.
What advice can you give for oral mucositis?
Good oral hygiene (rinsing the mouth frequently and effective brushing of the teeth with a soft brush 2–3 times daily) is probably beneficial. For fluorouracil, sucking ice chips during short infusions of the drug is also helpful.
Once a sore mouth has developed, treatment is much less effective.
In general, mucositis is self-limiting but with poor oral hygiene it can be a focus for blood-borne infection.
Which mouth wash should be used for oral mucositis?
Saline mouthwashes should be used but there is no good evidence to support the use of antiseptic or anti-inflammatory mouthwashes.
Which patients are at risk of tumour lysis syndrome?
include those with non-Hodgkin’s lymphoma (especially if high grade and bulky disease), Burkitt’s lymphoma, acute lymphoblastic leukaemia and acute myeloid leukaemia (particularly if high white blood cell counts or bulky disease), and occasionally those with solid tumours.
Pre-existing hyperuricaemia, dehydration, and renal impairment are also predisposing factors.
What are the features of tumour lysis syndrome?
Features include hyperkalaemia, hyperuricaemia (see below), and hyperphosphataemia with hypocalcaemia; renal damage and arrhythmias can follow. Early identification of patients at risk, and initiation of prophylaxis or therapy for tumour lysis syndrome, is essential.
Can chemotherapy worsen hyperuriceamia?
Yes - Hyperuricaemia, which may be present in high-grade lymphoma and leukaemia, can be markedly worsened by chemotherapy and is associated with acute renal failure.
What should be started in hyperuricaemia in chemotherapy?
- Allopurinol should be started 24 hours before treating such tumours and patients should be adequately hydrated
The dose of which proliferative immunosuppressants should be reduced if allopurinol is used?
The dose of mercaptopurine or azathioprine should be reduced if allopurinol needs to be given concomitantly.
Which other drug other than allopurinol can be used?
- Febuxostat may also be used and should be started 2 days before cytotoxic therapy is initiated
Which drug is licensed to be used for hyperuricaemia in patients with haematological malignancy?
Rasburicase, a recombinant urate oxidase, is licensed for hyperuricaemia in patients with haematological malignancy.
It rapidly reduces plasma-uric acid concentration and may be of particular value in preventing complications following treatment of leukaemias or bulky lymphomas.
Do all cytotoxic drugs cause bone-marrow supression?
Yes except vincristine sulfate and bleomycin.
Peripheral blood counts should be checked when?
Before each treatment and doses should be reduced or therapy delayed if bone-marrow has not recovered
What should be noted about cytotoxic drugs and active infection?
Cytotoxic drugs may be contra-indicated in patients with acute infection; any infection should be treated before, or when starting, cytotoxic drugs.
What does fever in neutropenic chemotherapy patient (neutrophil count less than 1.06x10^9/Litre) require?
Requires immediate broad-spectrum antibacterial therapy
What is symptomatic anaemia in chemotherapy patients usually treated with?
With red blood cell transfusions.
Is hair loss (alopecia) a complication of cytotoxic drugs?
Yes - it is a common complication, although it varies in degree between drugs and individual patients.
Is there a pharmacological method to prevent alopecia (hair loss) from chemotherapy?
No
Does chemotherapy increase the risk of thromboembolism?
Venous thromboembolism can be a complication of cancer itself, but chemotherapy increases the risk.
Due to teratogenicity what should be excluded before starting cytotoxic drug?
Exclude pregnancy
Contraceptive advice should be given before cytotoxic therapy begins- women of childbearing age should use effective contraception during and after treatment.
Which cytotoxic drugs carry a greater risk for causing permanent male sterility?
Regimens that do not contain an alkylating drug or procarbazine may have less effect on fertility, but those with an alkylating drug or procarbazine carry the risk of causing permanent male sterility (there is no effect on potency).
Pretreatment counselling and consideration of sperm storage may be appropriate.
Are women also equally affected?
No women are less severely affected, although the span of reproductive life may be shortened by the onset of a premature menopause
Is nausea and vomiting common with cytotoxic drugs?
Yes therefore prophylaxis of nausea and vomiting is extremely important
What is classed as acute symptom or delayed nausea and vomiting with chemotherapy?
Symptoms may be acute (occurring within 24 hours of treatment), delayed (first occurring more than 24 hours after treatment), or anticipatory (occurring prior to subsequent doses).
Which are more difficult to treat?
Delayed and anticipatory symptoms are more difficult to control than acute symptoms and require different management.
Which patients are more affected by nausea and vomiting with cytotoxic drugs?
- women
- patients under 50 years of age
- anxious patients
- those who experience motion sickness
Susceptibility also increases with repeated exposure to the cytotoxic drug.
Drugs may be divided according to their emetogenic potential - give some examples?
Mildly emetogenic treatment—fluorouracil, etoposide, methotrexate (less than 100 mg/m2, low dose in children), the vinca alkaloids, and abdominal radiotherapy.
Moderately emetogenic treatment—the taxanes, doxorubicin hydrochloride, intermediate and low doses of cyclophosphamide, mitoxantrone, and high doses of methotrexate (0.1– 1.2 g/m2).
Highly emetogenic treatment—cisplatin, dacarbazine, and high doses of cyclophosphamide.
For patients at low risk of emesis, pretreatment with which drugs may be used?
Dexamethasone or lorazepam
For patients at high risk of emesis what is usually given?
A 5HT3-receptor antagonist (e.g. ondansetron) usually given by mouth in combination with dexamethasone and the neurokinin receptor antagonist aprepitant is effective
What is used for the prevention of delayed emetic symptoms from chemotherapy?
For delayed symptoms associated with moderately emetogenic chemotherapy, a combination of dexamethasone and 5HT3-receptor antagonist is effective; for highly emetogenic chemotherapy, a combination of dexamethasone and aprepitant is effective. Rolapitant and metoclopramide hydrochloride are also licensed for delayed chemotherapy-induced nausea and vomiting.
What about for prevention of anticipatory symptoms?
Lorazepam can be helpful for its amnesic, sedative and anxiolytic effects
Anthracyclines are a class of drug used in chemotherapy - what induced side effects can these drugs cause?
Anthracycline-induced cardiotoxicity
The anthracycline cytotoxic drugs are associated with dose-related, cumulative, and potentially life-threatening cardiotoxic side-effects.
What is given for the speed recovery from methotrexate-induced mucositis or myelosuppression?
Folinic acid (given as calcium folinate)
‘Folinic acid rescue’
Folinic acid is also used for the treatment of methotrexate overdose, can it also be used for other folate antagonists such as trimethoprim?
No - Folinic acid does not counteract the antibacterial activity of folate antagonists such as trimethoprim
When fluorouracil is used in colorectal cancer what other drug is it given with?
When folinic acid and fluorouracil are used together in metastatic colorectal cancer the response-rate improves compared to that with fluorouracil alone.
Which other drug can be used for treatment of methotrexate overdose?
The calcium salt of levofolinic acid, a single isomer of folinic acid, is also used for rescue therapy following methotrexate administration, for cases of methotrexate overdose, and for use with fluorouracil for colorectal cancer. The dose of calcium levofolinate is generally half that of calcium folinate.
Why should radiotherapy be avoided simultaneously with some cytotoxic antibiotics?
Many cytotoxic antibiotics act as radiomimetics and simultaneous use of radiotherapy should be avoided because it may markedly increased toxicity
List examples of anthracycline antibiotics?
Daunorubicin, doxorubicin hydrochloride, epirubicin hydrochloride and idarubicin hydrochloride
What is doxorubicin used for?
Conventional doxorubicin hydrochloride is used to treat the acute leukaemias, Hodgkin’s and non-Hodgkin’s lymphomas, paediatric malignancies, and some solid tumours including breast cancer.
Whats the use of Epurubicin?
is structurally related to doxorubicin hydrochloride and can be used to treat breast cancer.
What is the use of idarubicin?
Idarubicin hydrochloride has general properties similar to those of doxorubicin hydrochloride; it is mostly used in the treatment of haematological malignancies.
What is the use of daunorubicin?
Daunorubicin also has general properties similar to those of doxorubicin hydrochloride.
Give examples of vinca alkaloids?
vinblastine sulfate, vincristine sulfate, and vindesine sulfate,
What are these vinca alkaloids used to treat?
are used to treat a variety of cancers including leukaemias, lymphomas, and some solid tumours
Which cytotoxic drug class is the most widely used in cancer chemotherapy?
Alkylating drugs
Give examples of alkylating drugs?
- Cyclophosphamide
- Ifosfamide
- Melphalan
- Lomustine
- Carmustine
- Estramustine
When is Estramustine phosphate usually used?
Estramustine phosphate is a combination of an oestrogen and chlormethine used predominantly in prostate cancer. It is given by mouth and has both an antimitotic effect and (by reducing testosterone concentration) a hormonal effect.
Which cytotoxic drug class does fluorouracil belong to?
Antineoplastic drugs (Antimetabolites)
Is bleomycin a cytotoxic antibiotic?
Yes - and it is one of two cytotoxic drugs that does not cause myelosuppression
Name the cytotoxic drugs that belong to the drug class - platinum compounds?
- Carboplatin
- Cisplatin
- Oxaliplatin
What route of administration is the only route that should be given for vinca alkaloids?
Intravenous route only
Intrathecal route can cause severe neurotoxicity, which is usually fatal
What has the national safety agenecy advised of patients receiving their vinca alkaloid?
Adult and teenage patients should receive their vinca alkaloid dose in a 50ml minibag.
Teenagers and children treated in a child unit may receive their vinca alkaloid dose in a syringe
What is the most common form of malignancy in women?
Breast cancer - especially in those over 50 years
What are the risk factors of breast cancer?
age, early onset of menstruation, late menopause, older age at first completed pregnancy, and a family history of breast cancer.
The use of oral contraceptives or hormone replacement therapy (HRT) is also associated with an increased risk of breast cancer.
Is breast cancer also common in men?
No it is rare in men
Although risk factors are not fully understood, it may be associated with abnormalities of sex hormone metabolism, including those caused by liver disease or testicular trauma, genetic predisposition, and environmental risk factors such as industrial exposure to chronic heat.
What are additional risk factors of breast cancer?
- Obesity and alcohol consumption
Which two things can protect against breast cancer?
- Physical activity and breast-feeding
What is non-invasive breast cancer also known as?
- Ductal carcinoma in situ
is when the cancer remains localised in the ducts
However, in most cases, the cancer is invasive at the time of diagnosis, which means that malignant cells are liable to spread beyond the immediate area of the tumour
What can invasive breast cancer be defined as?
Invasive breast cancer, where malignant cells spread beyond the ducts, can be defined as early breast cancer (stage I/II), locally advanced disease (stage III) and advanced disease (stage IV).
What is neoadjuvant drug therapy?
Drug treatment before surgery
What is the purpose of neoadjuvant drug therapy for breast cancer?
aims to reduce the size of the tumour to allow breast-conserving surgery to be possible and to reduce axillary lymph node involvement.
Is advanced breast cancer curable?
No and treatment aims to prolong survival, relieve symptoms and improve quality of life
What are the three types of management involved in breast cancer?
Surgery
Radiotherapy
Drug therapy
or a combination of these
In women with invasive breast cancer what is recommended?
Radiotherapy is recommended after breast conserving surgery with clear margins (no cancer cells are found at the edges of the removed tissues), as it reduces the local recurrence rates.
However, the use of radiotherapy may be omitted if risk of local recurrence is very low and the woman is willing to take adjuvant endocrine therapy for a minimum of 5 years.
What may adjuvant drug therapy for breast cancer include?
- chemotherapy
- Endocrine therapy
- Biological therapy
- Bisphosphonate therapy
In women with invasive breast cancer in only one breast who have not received treatment, including the use of neoadjuvant chemotherapy, NICE recommends the use of which tool to determine prognosis?
Recommends the use of the PREDICT tool to estimate prognosis and the absolute benefits of adjuvant therapy
What adjuvant chemotherapy is recommended in patients with invasive breast cancer who are at sufficient risk of disease recurrence to require chemotherapy?
Adjuvant anthracycline-taxane combination
Which biological therapy is used in breast cancer?
Trastuzumab
Tamoxifen should be used in which women?
Should be used as an initial endocrine therapy in men and premenopausal women with oestrogen-receptor positive invasive breast cancer
In addition suppression of what should be considered?
In addition, ovarian function suppression with a gonadotropin-releasing hormone (GnRH) should be considered in premenopausal women, taking into account the risk of temporary menopause. Ovarian function suppression aims to stop the production of circulating oestrogen, which can stimulate breast cancer progression.
It may be most beneficial in women who are at sufficient risk of disease recurrence to have been offered chemotherapy.
What about in postmenopausal women with oestrogen receptor positive invasive breast cancer who are at medium or high risk of disease recurrence?
an aromatase inhibitor should be given as first-line therapy. Alternatively, tamoxifen should be given if an aromatase inhibitor is not tolerated or is contra-indicated, or if the risk of disease recurrence is low.
how long is endocrine therapy as adjuvant therapy used for in breast cancer?
5 years
Can endocrine therapy for ductal carcinoma in situ be used?
Following breast-conserving surgery, endocrine therapy should be offered to women with oestrogen-positive ductal carcinoma in situ, if radiotherapy is recommended but not given. If radiotherapy is not recommended, the use of endocrine therapy should also be considered.
which bisphosphonate therapy can be used in breast cancer?
Zoledronic acid and sodium clodronate have been shown to improve disease-free survival and overall survival in postmenopausal women with node-positive invasive breast cancer. However, there is insufficient evidence to recommend their use in premenopausal women.
Who should neoadjuvant chemotherapy be offered to?
should be offered to reduce tumour size in patients with oestrogen-receptor-negative invasive breast cancer.
In patients with oestrogen-receptor-positive invasive breast cancer, chemotherapy should be considered. In patients with HER2-positive invasive breast cancer, neoadjuvant chemotherapy should be offered in combination with trastuzumab and pertuzumab.
What should be offered first line to post menopausal women with oestrogen-receptor positive advanced breast cancer?
Aromatase inhibitors should be offered to postmenopausal women with no previous history of endocrine treatment, or to those previously treated with tamoxifen.
What should be offered first line for pre- and perimenopausal women with oestrogen-receptor-positive advanced breast cancer?
Tamoxifen in combination with ovarian function suppression should be offered as first-line treatment to pre- and perimenopausal women with oestrogen-receptor-positive advanced breast cancer not previously treated with tamoxifen.
What should be offered first line to men with oestrogen-receptor-positive advanced breast cancer?
Tamoxifen
Which monoclonal antibody is recommended for the treatment of HER2-positive advanced breast cancer?
Trastuzumab
It is used in combination with paclitaxel in those who have not received chemotherapy for metastatic breast cancer, and as monotherapy for patients who have received at least two chemotherapy regimens for metastatic breast cancer
What should be offered to all women who have been identified as being at high-risk of developing breast cancer?
Chemoprevention
Should also be offered to women whoa are at moderate risk
How many years should chemoprevention be continued for?
For 5 years
Can anastrazole be given for chemoprevention of breast cancer to patients with severe osteoporosis?
No and instead tamoxifen can be given, provided there is no history or increased risk of thromboembolic disease or endometrial cancer
What can some treatments used in the management of breast cancer such as tamoxifen or ovarian function suppression lead to?
may lead to menopausal symptoms or early menopause, and women should be counselled about these side-effects prior to starting any of these treatments.
What should happen to a woman’s HRT if they are diagnosed with breast cancer?
It should be discontinued;
HRT should not be offered routinely to women with menopausal symptoms if they have a history of breast cancer;
however, in exceptional circumstances, HRT can be offered to women with severe menopausal symptoms once the associated risks have been discussed
What drug class can be offered to treat menopausal symptoms such as hot flushes in women with breast cancer who are not taking tamoxifen?
SSRIs (Selective serotonin reuptake inhibitors)
.Clonidine hydrochloride, venlafaxine [unlicensed indication] and gabapentin [unlicensed indication] are sometimes used for the treatment of hot flushes in women with breast cancer after discussion with the patient and information given about side effects.
What is the most common cancer affecting men?
Prostate cancer
Can prostate cancer also affect transgender women?
Yes as the prostate is usually conserved after gender confirming surgery
What are the main risk factors of prostate cancer?
- most cases being diagnosed in men over 70 years of age
- ethnicity (more common in black African-Caribbean men)
- Obesity
- Familial component
Is prostate cancer a fast growing or slow growing disease?
usually Slow growing
Is prostate cancer symptomatic or asymptomatic at diagnosis?
usually Asymptomatic
What are the presenting symptoms of advanced disease of prostate cancer?
- urinary outflow obstruction
- pelvic or back pain due to bone metastases
What are the treatment options for prostate cancer?
Active surveillance, prostatectomy, radiotherapy (such as external beam), brachytherapy, hormone therapy, and chemotherapy. The benefits and risks of each option should be discussed with patients.
What hormone therapy are included in managing prostate cancer?
Hormone therapy includes anti-androgen therapy—to block the effects of androgens, androgen deprivation therapy such as a luteinising hormone-releasing hormone (LHRH) agonist, or a gonadorelin antagonist—to reduce androgen levels, and bilateral orchidectomy—to remove the endogenous supply of androgens.
For patients with low-risk localised prostate cancer what should be offered?
offer a choice between active surveillance, radical prostatectomy or radiotherapy.
Radical treatment should be offered to patients with localised prostate cancer undergoing active surveillance who show evidence of disease progression.
What should be offered to patients with intermediate risk localised prostate cancer?
radical treatments (prostatectomy or radiotherapy) should be offered, and for those who decline them, active surveillance can be considered.
What should be offered in those with high risk localised prostate cancer?
(when there is a realistic prospect of long-term disease control), and in those with locally advanced disease, radical prostatectomy or radiotherapy should be offered.
In patients with intermediate‐risk and high-risk localised prostate cancer who have chosen radical radiotherapy, what should this be accompanied by?
In combination with androgen deprivation therapy
How long should androgen deprivation therapy be given for?
Androgen deprivation therapy should be given for 6 months before, during or after radiotherapy; in patients with high‐risk localised prostate cancer, consider continuing therapy for up to 3 years.
In patients with hormone-relapsed non-metastatic prostate cancer who are at high risk of developing metastatic disease what should be given?
darolutamide or apalutamide, with androgen deprivation therapy is recommended as a treatment option.
What side effects may patients experience of prostate cancer treatment?
Patients should be informed about the side-effects of treatment; particularly urinary and sexual dysfunction, loss of fertility, radiation-induced enteropathy, osteoporosis, gynaecomastia, fatigue, and hot flushes.
Patients who are on androgen deprivation therapy should be offered what?
A supervised exercise program (at least twice a week for 12 weeks) to reduce fatigue and improve quality of life.
Should a bisphosphonate be offered to patients who have osteoporosis who are having androgen deprivation therapy?
Yes -A bisphosphonate should be offered to patients who have osteoporosis and who are having androgen deprivation therapy; denosumab is an alternative if bisphosphonates are not appropriate.
What can occur with long term (longer than 6 months) bicalutamide treatment?
Gynaecomastia
Is tamoxifen an anti-androgen?
Yes
Effective contraception should be used during tamoxifen treatment and how many months after?
2 months after
What drug class does anastrazole belong to?
Aromatase inhibitor
What is the dose of anastrozole in chemotherapy of breast cancer?
1mg daily
What is the dose of tamoxifen in chemotherapy of breast cancer?
20mg daily
Does tamoxifen affect risk of throboembolism?
Yes - particulary during and immediately after major surgery r periods of immobility (consider interrupting treatment and initiating anticoagulant treatment)
Other than anastrazole which other aromatase inhibitor is used for breast cancer?
Letrozole
What is the dose of letrozole in chemotherapy in breast cancer treatment?
2.5mg daily
Can thalidomide be used in pregnancy?
100% no - important teratogenic risk
If rash occurs with thalidomide what should happen?
Stop treatment
Does tamoxifen affect endometrial cancer risk?
Yes it increases endometrial cancer risk
Patients should report abnormal vaginal bleeding including menstrual irregularities, vaginal discharge and pelvic pain/pressure
What is extravasation injury?
- A number of cytotoxic drugs will cause severe local tissue necrosis if leakage into the extravascular compartment occurs. To reduce the risk of extravasation injury, cytotoxic drugs should be administered by appropriately trained staff.
Why does tumour lysis syndrome occur?
- Tumour lysis syndrome occurs due to rapid destruction of malignant cells (due to the drug or spontaneously). Features include hyperkalaemia, hyperuricaemia and hyperphosphataemia with hypocalcaemia. Renal damage and arthritis can follow.
Which type of vaccines should patients on immunosuppressants avoid?
Avoid Live vaccines
What is the MAO of azathioprine/mercaptopurine?
Azathioprine is metabolised to mercaptopurine
Mercaptopurine inhibits purine metabolism therefore DNA, RNA and protein synthesis.
Why does dose of azathioprine/ mercaptopurine need to be reduced if given together with allopurinol?
Because allopurinol is a xanthine oxidase inhibitor; inhibits metabolism of purines
Which is more selective, mycophenolate or azathioprine?
Mycophenolate is more selective
What is a side effect of mycophenolate which is indicated by recurrent infections?
Hypogammaglobinaemia
Recurrent infections = measure serum immunoglobulin
how long is contraception required for mycophenolate?
Women - two methods of effective contraception until 6 weeks after discontinuing
Men - use condom until 90 days after discontinuing OR female partners of male patients use effective contraception until 90 days
What can tacrolimus affect in the blood?
Blood pressure
Hyperglycaemia
Hyperkalaemia
Hyperuricaemia
What symptoms can indicate tacrolimus induced neurotoxicity?
- Headaches and tremors
What about diet should patients be advised who are taking tacrolimus?
Avoid high potassium and grapefruit juice = high tacrolimus level
What does ciclosporin lower the activity of?
Lowers activity of T cells and their immune response
Can ciclosporin cause gingival hyperplasia?
Yes
What patient counselling should be given for ciclosporin?
- Avoid excess sun exposure/ UV light: use wide spectrum SPF
- Diet : avoid high potassium and grapefruit juice = high ciclosporin level
List the overall side effects of cytotoxic drugs?
- Thromboembolism (increased risk)
- Hyperuricaemia
- Alopecia
- Nausea and vomiting
- Bone marrow suppression
- urothelial toxicity
- Oral mucositis
- Pregnancy and reproductive function
Which cytotoxic drugs cause permanent male sterility?
Alkylating drugs and procarbazine
Counsel patients on sperm storage
Women are less affected - early menopause may occur
Describe what is tumour lysis syndrome?
- caused by rapid destruction of malignant cells (high risk in lymphomas or leukaemias)
What is the clinical features of tumour lysis syndrome?
- hyperkalaemia
- hyperuricaemia
- Hyperphosphatemia
- Hypocalcaemia
this is followed by renal failure and arrhythmias
Which patients are at risk of tumour lysis syndrome?
Renal impairment
Dehydration
Hyperuricaemia
Which cytotoxic drugs cause oral mucositis?
- Anthracyclines
- Antimetabolites (methotrexate, Fluoruracil, Capecitabine)
What is haemorrhagic cystitis?
Urothelilal toxicity =
Hemorrhagic cystitis - Which is an inflammation of the bladder defined by lower urinary tract symptoms that include dysuria, hematuria, and hemorrhage
What is the drug used to treat urothelial toxicity?
Mesna
Which cytotoxic drug is known to cause urothelial toxicity?
Cyclophosphamide (Alkylating drug)
All cytotoxic drugs cause bone marrow suppression except which two?
vincristine
bleomycin
If patient has fever with neutropenia and is on an immunosuppressant then what should be given?
- broad spectrum antibiotic
Avoid paracetamol as it delays starting an antibiotic
Which drug can be used to treat neutropenia associated with cancer medications?
Filgrastrim
Hyperuricaemia is present in which types of cancers?
high grade lymphomas and leukaemia
markedly worsened by chemotherapy and associated with renal failure
Which drugs can be used to treat hyperuricaemia in chemotherapy or cancer patients?
Allopurinol - 24 hours before treating such tumours, reduce dose of concomitant mercaptopurine/ azathioprine
Febuxostat - 2 days before if allopurinol contraindicated or not tolerated
Rasburicase - for hyperuricaemia associated with blood cancer (provides rapid decrease)
Which cytotoxic drugs are mild emetogenics (cause nausea and vomiting)?
Methotrexate
Fluorouracil
Vinca Alkaloids
Which cytotoxic drugs are moderate emetogenics?
Taxanes
Doxorubucin
Cyclophosphamide
High-dose MTX
Which cytotoxic drugs are high emetogenics?
Cisplatin
High-dose cyclophosphamide
Which drug can be used for anticipatory (before treatment) (thought of feeling sick) for chemotherapy?
Lorazepam
What about acute symptoms (N+V) that are within 24 hours after chemotherapy?
Low risk of emesis= dexamethasone or lorazepam
High risk of emesis = Dexamethasone + 5-HT3 antagonist, aprepitant
What is the treatment for delayed symptoms (N+V) more than 24 hours after chemotherapy?
Moderately emetogenic drugs = dexamethasone + 5HT3 antagonist
Highly emetogenic drugs = dexamethasone + Aprepitant
Is alopecia associated with chemotherapy permanent?
No it is reversible hair loss - common complication of chemotherapy
Is there a treatment available to prevent chemotherapy induced alopecia?
No
What is extravasation of IV cytotoxic drugs?
- Severe local tissue necrosis - if the drugs leak from the veins into the surrounding subcutaneous or subdermal tissue
(In worse cases it can lead to amputation)
Which cytotoxic drugs are more prone to extravasation of IV drugs?
Vinca Alkaloids
Anthracyclines
Do cytotoxic antibiotics radiomimetic?
Yes they are, therefore avoid concomitant radiotherapy = toxicity
What are the two classes of cytotoxic antibiotics?
- Anthracyclines
- Antineoplastic Antibiotics
What is a good way to remember anthracyclines?
‘RUBICIN’
List the anthracyclines?
- Doxorubicin
- Epirubicin
- Idarubicin
- Daunorubicin
How is doxorubicin excreted?
Excreted in bile - reduce dose if high bilirubin
What is a side effect of anthracyclines?
- Cardiotoxicity (dose related: higher risk if given with herceptin)
What colour does the urine be discoloured with anthracyclines e.g. Doxorubicin?
Red colour
What do liposomal formulations of doxorubicin reduce incidence of?
Reduce incidence of cardiotoxicity and extravasation BUT cause:
- Hand and Foot syndrome (Macular, red skin eruptions)
Liposomal formulations of doxorubicin can cause hand and foot syndrome - what advice can you give?
Prevention:
Cool hands and feet and avoid socks and gloves for 4-7 days after treatment
What is given as an antidote to anthracyclines?
Dexrazoxane -
is given for anthracycline-induced side effects, extravasation and overdose
List an example of a antineoplastic antibiotic?
- Bleomycin
What are some important side effects of bleomycin?
- Pulmonary Fibrosis = basal lung crapitations
- Respiratory failure in anaesthesia
- Hypersensitivity = chils and fever
Prevention: IV hydrocortisone
Dermatological toxicity = hyperpigmentation, sclerotic plaques
List the drugs that are vinca alkaloids?
- Vincristine
- Vinblastine
- Vindesine
- Vinflunine
- Vinorelbine
What route of administration is the only one allowed for vinca alkaloids?
Intravenous route only
What is the risk of giving vinca alkaloids intrathecally?
Fatal neurotoxicity
How should adults and teenagers unit receive their doses of vinca alkaloids in?
- In a 50ml mini bag
How should children’s unit receive doses in?
doses by syringes
What is the general side effect of vinca alkaloids?
CNS toxicity (peripheral/autonomic neuropathy)
Which cytotoxic drugs are known as antimetabolites?
- Methotrexate (MTX)
- Capecitabine (Pro-drug of 5-FU)
- Florouracil (5-FU)
What is the main side effects of cytotoxic antimetabolites?
Oral mucositis
Myelosuppression
Which drug speeds up recovery in MTX side effects and overdose?
Folinic acid
List cytotoxic drugs classed as the alkylating drugs?
- Cyclophosphamide (causes urothelial toxicity)
- Carmustine
- Lomustine
- Mephalan
- Chlorambucil
- Isosfamide
What is the important side effects of alkylating drugs?
- Permanent male sterility
- Non-lymphocytic leukaemia
List the two aromatase inhibitors used in the treatment of breast cancer?
- Anastrazole
- Letrozole
Can aromatase inhibitors be used for pre-menopausal women?
No they cannot be used for pre-menopausal women as aromatase inhibitors are ‘anti-oestrogens’
Give an example of a cytotoxic drug from the class Taxane?
- Paclitaxel
What are the main side effects of taxane cytotoxic drugs?
- Cardiac disease
- Pneuomonitis
- Sepsis
