Chapter 8: Immune system and malignant disease Flashcards
What are main side effects of azathioprine?
- Hypersensitivity reactions - fever, rash
- Neutropenia and thrombocytopenia
- Nausea
- Myelosuppression
What pre-treatment screening is needed with azathioprine?
Thiopurine S-methyltransferase (TPMT) deficiency = reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system. TPMT metabolises the drug, so with reduced levels, there is an increased risk of myelosuppression
What is the MHRA advice regarding ciclosporin prescribing?
Must be prescribed and dispensed by BRAND name
What is the MHRA advice surrounding tacrolimus prescribing? Calcineurin inhibitors (CNI) are a family of three drugs (cyclosporine, tacrolimus, and pimecrolimus) that clinicians can use to suppress the immune system
Prescribe and dispense by BRAND name only, to minimise risk of inadvertent switching between products => reports of toxicity and graft rejection
When monitoring tacrolimus, should peak or trough levels be taken?
Trough for Tacrolimus
Especially when there is diarrhoea, levels need to be closely monitored
What is the MHRA advice surrounding the use of mycophenolic acid/MMF?
Monitoring requirements?
MHRA
- exclude pregnancy in females before tx —2 preg tests 8–10 days apart are recommended.
- Women should use at least 1 method of effective contraception before and during treatment, and for 6 weeks after discontinuation - 2 are preferred.
- genotoxic
- contraindicated in women of childbearing potential without reliable contraception and in pregnant women unless no suitable alt to prevent transplat rejection
- Male patients or their female partner should use effective contraception during treatment and for 90 days after discontinuation.
Monitoring: Monitor FBC every week for 4 weeks then twice a month for 2 months then every month in the first year (consider interrupting tx if neutropenia develops).
Fingolimod, a drug used for MS, carry what MHRA warnings?
- Signal of rebound effect after stopping or switching therapy
- Not rec for patients at known risk of CVS events e.g. persistent bradycardia
- Has an immunosuppressive effect and can ^! skin cancers and lymphoma - refer pts with any skin lesions
What is the MHRA advice surrounding the use of bevacizumab?
Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor.
- Treatment with bevacizumab or sunitinib may be a risk factor for the development of osteonecrosis of the jaw.
- Systemically administered VEGF pathway inhibitors: risk of aneurysm and artery dissection
- at risk if pt on tx with bevacizumab or sunitinib also took/taking bisphosphonates; Dental examination and appropriate preventive dentistry considered before treatment.
- If possible, invasive dental procedures should be avoided in patients treated with bevacizumab or sunitinib who have previously received, or who are currently receiving, intravenous bisphosphonates
- The MHRA advises to monitor blood pressure regularly
What is the MHRA advice surrounding the use of EGFR inhibitors e.g. cetuximab?
Epidermal growth factor receptor (EGFR) inhibitors: serious cases of keratitis and ulcerative keratitis
In rare cases, this has resulted in corneal perforation and blindness
What is the MHRA advice surrounding the use of nivolumab?
Risk of organ transplant REJECTION
Which two cytotoxic drugs do not cause bone marrow suppression?
Vincristine
Bleomycin
Ciclosporin can cause what kinds of toxicity?
Neurotoxicity
Nephrotoxicity
What is the patient advice surrounding ciclosporin?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
Tacrolimus can cause what kinds of organ damage?
Nephrotoxicity Cardiomyopathy Neurotoxicity - headaches, tremors Hepatotoxicity Eye disorders- burred vision
Can also disturb glucose metabolism
What is the patient advice surrounding tacrolimus?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
What is a local reaction that can happen when IV cytotoxics are given?
Extravasation - severe local tissue necrosis
What are the main side effects of cytotoxics?
- Alopecia
- n+v
- Oral mucositis - imp. to maintain good oral hygiene
- Tumour lysis syndrome
- HyperUricaemia - this is associated with acute renal failure. Give allopurinol/rasburicase
- Bone marrow suppression apart from vincristine and bleomycin
- Thromboembolism - cancer itself increases this risk too
What are the features of tumour lysis syndrome?
HyperKalaemia, hyperUricaemia, hyperPHosphataemia with
hypocalcaemia; renal damage and arrhythmias
How is acute nausea and vomiting symptoms managed in low risk chemotherapy patients?
Dexamethasone or lorazepam
How is acute nausea and vomiting symptoms managed in high risk chemotherapy patients?
5HT3 antagonist e.g. ondansetron + dexamethasone + aprepritant
What is used for prevention of anticipatory nausea and vomiting in chemotherapy patients?
Symptomatic control
Lorazepam can help
Which cytotoxic drug class has a high risk of cardiotoxicity and how is this prevented?
Anthracyclines - doxorubicine, epirubicine
An iron chelate derazoxane is given
What is given to counteract the folate-antagonist action of methotrexate in chemotherapy?
Folinic acid (calcium folinate)
This is also used in overdose but does not work for antibiotics with anti-folate action e.g. trimethoprim
Mesna is given with what cytotoxic drugs and why?
Cyclophosphamide and ifosdamide
Prevents haemorhaegic cystitis as metabolites of the drugs cause a toxin (acrolein)
Cyclophosphamide and ifosfomide carry a risk of what?
What is done to prevent this?
Haemorrhaegic cystitis
MESNA is given to prevent urinary tract toxicity and increasing fluid intake for 24-48 hours after administration
What colour does doxorubicin turn your urine?
Red
Do normal or liposomal formulations of doxorubicin carry a higher risk of cardiotoxicity?
Normal formulations carry a higher risk
What monitoring needs to be done before starting doxorubicin?
ECG due to the cardiotoxicity
Monitor during treatment too
What are the main side effects of bleomycin?
- Hypersensitivity reactions
- Progressive pulmonary fibrosis - monitor for suspicious X-ray changes
- Respiratory failure
Should vinca alkaloids e.g. vincristine, vinblastine, be given IV or intrathecally?
Only ever IV
Intrathecal administration is associated with severe neurotoxicity
What is the patient advice surrounding methotrexate?
- Weekly dose not daily
- The patient must report any signs of blood disorders i.e. sore throat, bruising, mouth ulcers), liver toxicity (i.e. nausea, vomiting, abdominal pain and dark urine) and respiratory effects (SOB).
What are the serious side effects of methotrexate?
- Immunosuppression and blood disorders
- GI toxicity
- Stomatitis - inflammation of mouth and lips
- Liver toxicity
- Pulmonary toxicity
How is it recommended that methotrexate tablets are dispensed?
Single strength tablets only to avoid confusion, usually 2.5mg tablets
What is the MHRA warning regarding the use of imatinib?
Imatinib is a tyrosine kinase inhibitor.
An EU wide review has concluded that imatinib can cause hepatitis B reactivation; the MHRA recommends establishing hepatitis B virus status in all patients before initiation of treatment.
What is the first sign of methotrexate GI toxicity?
Stomatitis
Inflammation of mouth and lips
What are the pre-treatment screening requirements for methotrexate?
Exclude pregnancy before treatment
FBC, renal function and LFTs
What needs to be monitored in a patient on methotrexate and how often?
Have full blood count and renal and liver function tests repeated every 1–2 weeks until therapy stabilised, thereafter patients should be monitored every 2–3 months
What OTC medicines should a patient on methotrexate not have?
NSAIDs - aspirin, ibuprofen. It is thought that NSAID-induced inhibition of prostaglandin synthesis => reduced renal perfusion, => reduces renal excretion of MTX.
Patients should be counselled on the use of NSAIDs:
Report any symptoms suggestive of infection or blood dyscrasias (eg, sore throat, bruising or mouth ulcers), symptoms of liver impairment (eg, nausea, vomiting or dark urine), and any dyspnoea or cough, which can suggest pulmonary toxicity.
True or false:
Penicillins increase toxicity risk of methotrexate
True
How does allopurinol and azathioprine/mercaptopurine interact?
Azathioprine/mercaptopurine inhibits purine metabolism
Allopurinol also does this
Reduced dose is needed if given with allopurinol to reduce risk of toxicity
What are the main side effects of MMF to look out for?
Bone marrow suppression
Hypogammaglobinaemia - measure serum immunoglobulin if experiencing recurrent infections
Bronchiectasis - Look out for cough, SOB
What does the MHRA suggest for excluding pregnancy when starting MMF?
The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy tests 8–10 days apart are recommended.
Pregnancy prevention programme
What kind of juice should be avoided if on tacrolimus?
Grapefruit juice
What is neoadjuvant chemotherapy?
Delivered before the main treatment e.g. to shrink the tumour
What role does febuxostat play in chemotherapy patients?
Prophylaxis and treatment of acute hyperuricaemia
Started 2 days before chemo
Rasburicase is used for the treatment of acute hyperuricaemia in what kind of cancer?
Blood cancers
What is a common side effect of doxurubicin (more common with liposomal formulations)?
Hand-foot syndrome (painful, macular reddening skin eruptions) occurs commonly with liposomal doxorubicin and may be dose limiting. It can occur after 2–3 treatment cycles and may be prevented by cooling hands and feet and avoiding socks, gloves, or tight-fitting footwear. It may also occur with non-liposomal formulations
What biomarker can you measure to see if you need to reduce the dose of doxorubicin?
Doxorubicin largely excreted in bile and an elevated bilirubin concentration is an indication for reducing the dose.
What bags should vincristine and vinblastine go in for adults and teenagers to prevent it from being administered intrathecally?
50mL mini bag
Should also have a sticker on to say “For IV use only”
What is the contraception advice for men and women on methotrexate?
Use effective contraception for at least 6 months after treatment.
What is the advice surrounding the use of ciclosporin and malignancies?
Like other immunosuppressants, ciclosporin ^ risk of developing lymphomas + other malignancies, esp skin.
In psoriasis, exclude malignancies (including those of skin and cervix) before starting.
It is CI in malignancy for non-transplant indications (can be used in UC, RA, psoriasis)
Can chemotherapy prescriptions be on repeat?
Prescriptions should not be repeated except on the instructions of a specialist.
Dose is dependent each time on a lot of factors e.g. blood count
How is delayed n+v symptoms managed in moderate risk chemotherapy patients?
Ondansetron and Dexamethasone
How is delayed n+v symptoms managed in high risk chemotherapy patients?
Dexamethasone + aprepitant
Also licensed: Metoclopramide, Rolapitant
Is cyclizine used for n+v in chemo patients?
No - it is not licensed
This is mainly used for post op and palliative care N+V
Can metoclopramide be used in acute N+V in chemo patients?
No, only licensed in the delayed phase (>24 hrs of symptom onset)
Is it recommended to have a chest X Ray before methotrexate treatment?
Not usually indicated.
Patients should have full blood count and renal and liver function tests before starting treatment. as well as pregnancy test.
What are the 3 UK cancer screening programmes?
Breast - Bowel - Cervical
Is there a screening programme for prostate cancer?
No
Because PSA test is not reliable enough, but men > 50 can ask their doctor about it.
What is the bowel cancer screening programme e.g. age, what does the patient need to do, how often, what gender?
In England, between ages of 60 and 74 yrs.
- Both male and female
- Every 2 years
- Send off a stool sample
- Registered with a GP to receive screening invitations
What is the breast cancer screening programme e.g. age, how often, what does the patient need to do,?
50-70 years
In some areas this extends from 47 to 73 years
- Every 3 years
- Mammogram
You need to be registered with a GP to receive screening invitations
What is the cervical cancer screening programme e.g. age, how often?
25-49 years every 3 years
49-64 years every 5 years
Need to be registered with GP
Patients vary in their susceptibility to drug-induced nausea and vomiting; those affected more often include ..?
Patients vary in their susceptibility to drug-induced nausea and vomiting; those affected more often include women, patients < 50 years of age, anxious patients, and those who experience motion sickness. Susceptibility also increases with repeated exposure to the cytotoxic drug
What is the emetogenic potential of the following drugs?
- MTX
- vinca alkaloids (vinblastine/vincristine)
- doxorubicin
- cisplatin
- cyclophosphamide
MILD emetogenic tx—fluorouracil, etoposide, methotrexate (less than 100 mg/m2, low dose in children), vinca alkaloids, and abdominal radiotherapy.
MODERATE emetogenic tx—the taxanes, doxorubicin hcl, intermediate and low doses of cyclophosphamide, mitoxantrone, and high doses of MTX.
Highly emetogenic treatment—cisplatin, dacarbazine, and high doses of cyclophosphamide.
For patients at low risk of emesis, pretreatment with
dexamethasone or lorazepam
How to prevent anticipatory symptoms of n+v? chemo
Good symptom control is the best way to prevent anticipatory symptoms. Lorazepam can be helpful for its amnesic, sedative, and anxiolytic effects.
Rasburicase contraindication?
Rasburicase catalyzes enzymatic oxidation of poorly soluble uric acid into an inactive and more soluble metabolite allantoin with carbon dioxide and hydrogen peroxide as byproducts in the chemical reaction.
G6PD deficiency
