Chapter 8: Immune system and malignant disease Flashcards by Jonathan Daniel Kennedy

What are some main side effects of azathioprine?

Hypersensitivity reactions - fever, rash
Neutropenia and thrombocytopenia
Nausea

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What pre-treatment screening is needed with azathioprine?

TPMT levels

TPMT metabolises the drug, so if reduced levels, there is an increased risk of myelosuppression

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What is the MHRA advice regarding ciclosporin prescribing?

Must be prescribed and dispensed by brand name

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What is the MHRA advice surrounding tacrolimus prescribing?

Prescribe and dispense by brand name only, to minimise the risk of inadvertent switching between products, which has been associated with reports of toxicity and graft rejection

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When monitoring tacrolimus, should peak or trough levels be taken?

Trough

Especially when there is diarrhoea, levels need to be closely monitored

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What is the MHRA advice surrounding the use of mycophenolic acid/MMF?

The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy 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

Mycophenolate medicines remain contraindicated in women of childbearing potential who are not using reliable contraception and in pregnant women unless there are no suitable alternatives to prevent transplant rejection

Male patients or their female partner should use effective contraception during treatment and for 90 days after discontinuation.

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Fingolimod, a drug used for MS, carry what MHRA warnings?

Signal of rebound effect after stopping or switching therapy
Not recommended for patients at known risk of cardiovascular events e.g. persistent bradycardia
Has an immunosuppressive effect and can increase the risk of skin cancers and lymphoma - refer patients with any skin lesions

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What is the MHRA advice surrounding the use of bevacizumab?

Risk of osteonecrosis of the jaw

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What is the MHRA advice surrounding the use of EGFR inhibitors e.g. cetuximab?

Keratitis and ulcerative keratitis

In rare cases, this has resulted in corneal perforation and blindness

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What is the MHRA advice surrounding the use of nivolumab?

Risk of organ transplant rejection

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Which two cytotoxic drugs do not cause bone marrow suppression?

Vincristine

Bleomycin

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Ciclosporin can cause what kinds of toxicity?

Neurotoxicity

Nephrotoxicity

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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

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Tacrolimus can cause what kinds of organ damage?

Nephrotoxicity
Cardiomyopathy
Neurotoxicity - headaches, tremors
Hepatotoxicity
Eye disorders- burred vision

Can also disturb glucose metabolism

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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

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What is a local reaction that can happen when IV cytotoxics are given?

Extravasation - severe local tissue necrosis

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What are the main side effects of cytotoxics?

Alopecia
Nausea and vomiting
Oral mucositis - important to maintain good oral hygiene
Tumour lysis syndrome (due to destruction of malignant cells)
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

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What are the features of tumour lysis syndrome?

Hyperkalaemia, hyperuricaemia, hyperphosphataemia with

hypocalcaemia; renal damage and arrhythmias

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How is acute nausea and vomiting symptoms managed in low risk chemotherapy patients?

Dexamethasone or lorazepam

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How is acute nausea and vomiting symptoms managed in high risk chemotherapy patients?

5HT3 antagonist e.g. ondansetron + dexamethasone + aprepritant

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What is used for prevention of anticipatory nausea and vomiting in chemotherapy patients?

Symptomatic control

Lorazepam can help

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Which cytotoxic drug class has a high risk of cardiotoxicity and how is this prevented?

Anthracyclines - doxorubicine, epirubicine

An iron chelate derazoxane is given

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What is given to counteract the folate-antagonist action of methotrexate in chemotherapy?

Folinic acid (calcium folinate)

This is also used in methotrexate overdose but does not work for antibiotics with anti-folate action e.g. trimethoprim

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Mesna is given with what cytotoxic drugs and why?

Cyclophosphamide and ifosdamide

Prevents haemorhaegic cystitis as metabolites of the drugs cause a toxin (acrolein)

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Cyclophosphamide and ifsfomide 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?

Can cause reactivation of Hepatitis B

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 Patients should be counselled on the use of NSAIDs

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 May be prevented by cooling hands and feet and avoiding socks, gloves, or tight-fitting footwear

What biomarker can you measure to see if you need to reduce the dose of doxorubicin?

Doxorubicin is largely excreted in the 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 increases the risk of developing lymphomas and other malignancies, particularly those of the skin. In psoriasis, exclude malignancies (including those of skin and cervix) before starting It is contraindicated in malignancy for non-transplant indications (can be used in UC, RA, psoriasis)

Can chemotherapy prescriptions be on repeat?

No unless indicated by a specialist Dose is dependent each time on a lot of factors e.g. blood count

How is delayed nausea and vomiting symptoms managed in moderate risk chemotherapy patients?

Ondansetron and dexamethasone

How is delayed nausea and vomiting symptoms managed in high risk chemotherapy patients?

Dexamethasone + aprepitant Metoclopramide and rolapitant also licensed

Is cyclizine used for nausea and vomiting 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

Is it recommended to have a chest X Ray before methotrexate treatment?

Not usually indicated

What are the 3 UK cancer screening programmes?

Breast Bowel Cervical There is no screening programme for prostate cancer because the PSA test is not reliable enough, but men over 50 can ask their doctor about it.

Is there a screening programme for prostate cancer?

There is no screening programme for prostate cancer because the PSA test is not reliable enough, but men over 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, people between the ages of 60 and 74 years take part. Both male and female Every 2 years Send off a stool sample You need to be 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