Caution with oral anti-cancer drugs
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Select links for information on the safe prescribing, dispensing and administration of orally administered anti-cancer drugs.
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Venous access required
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IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.
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Hypersensitivity/infusion related reaction
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High risk with avelumab.
Severe infusion-related reactions have been reported.
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Premedication
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Premedicate with appropriate antihistamine and paracetamol prior to the first four infusions of avelumab. Further premedication is at the discretion of the treating physician. Premedication should continue if previous mild/moderate infusion related reaction.
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Emetogenicity minimal or low
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No routine prophylaxis required. If patients experience nausea and/or vomiting, consider using the low emetogenic risk regimen.
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Immune-related adverse events (irAEs)
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Immune-related adverse events (irAEs) can occur early and escalate quickly in patients receiving immune checkpoint inhibitors. irAEs can also occur after discontinuation of treatment. Fatalities have been reported. Management of irAEs is largely based on expert opinion and consensus guidelines.
Examples of irAEs with high risk of mortality include:
- cardiac toxicity: myocarditis
- musculoskeletal toxicity: myositis
- neurological toxicity: encephalitis, Guillain-Barré syndrome, myelitis, myasthenia gravis
- pulmonary toxicity: pneumonitis
- skin toxicity: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Examples of irAEs in order of frequency include:
- Common
- endocrinopathies: thyroid dysfunction
- gastrointestinal toxicity: diarrhoea
- musculoskeletal toxicity: arthralgia, myalgia
- skin toxicity: rash, erythema, pruritus
- Less common
- endocrinopathies: hypophysitis, type I diabetes mellitus
- gastrointestinal toxicity: colitis
- musculoskeletal toxicity: inflammatory arthritis
- ocular toxicity: dry eye
- renal toxicity
- skin toxicity: vitiligo
- Rare
- endocrinopathies: primary adrenal insufficiency
- gastrointestinal toxicity: pancreatitis
- haematological toxicity
- musculoskeletal toxicity: vasculitis
- ocular toxicity: uveitis, iritis.
Proactive monitoring, patient self-monitoring and early reporting of adverse events is critical. Treatment interruptions/discontinuation, consultation with specialist and administration of corticosteroids and/or supportive care is required to minimise the risk of death.
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Cardiac toxicity
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Tyrosine kinase inhibitors have been associated with cardiac complications of varying degrees and severity.
Patients, especially those with pre-existing cardiovascular disease, should have a baseline cardiac assessment including an electrocardiogram (ECG) and biochemistry and be closely monitored; consider an echocardiogram (ECHO) as clinically indicated.
Cardiac assessment should then be repeated as clinically indicated or when starting new medication which affects the QT interval.
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Thromboembolism
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Both arterial and venous thromboembolic events have been observed in patients with this treatment.
Therefore, use with caution in patients at increased risk or with a history of thrombotic events (i.e., cerebrovascular and cardiovascular disease)
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Haemorrhage
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Significant haemorrhagic events have occurred with this treatment.
Use with caution in patients with risk of haemorrhage (i.e. CNS metastases, coagulopathy, concurrent anticoagulant or antiplatelet medications etc.)
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Gastrointestinal perforation
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Serious cases of gastrointestinal (GI) perforation have been reported with this treatment. Use with caution in patients at risk of GI perforation. Patients should be monitored for signs and symptoms of GI perforation.
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Hypertension
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Pre-existing hypertension should be adequately controlled prior to commencing treatment. Baseline blood pressure monitoring and repeated weekly for the first 6 weeks then regularly throughout treatment.
In severe or uncontrolled hypertension, treatment should be withheld until hypertension is controlled. Dose modification or permanent discontinuation may be necessary - refer to dose modification section for specific recommendations.
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Hand-foot syndrome
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Hand-foot syndrome (palmar-plantar erythrodysaesthesia) and rash are common adverse effects with this treatment which generally appear during the first 6 weeks of therapy.
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Proteinuria
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Patients with a history of diabetes, high blood pressure and kidney disease may be at increased risk of developing proteinuria. Signs of proteinuria include swelling of the feet or the whole body.
Baseline and periodic urinalyses are recommended as clinically indicated.
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Hypothyroidism
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Thyroid dysfunction in particular hypothyroidism may occur with this treatment. Monitor for signs and symptoms of thyroid dysfunction and manage as clinically appropriate.
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Reversible posterior leukoencephalopathy syndrome (RPLS)
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Reversible posterior leukoencephalopathy syndrome (RPLS) has been reported in patients receiving this treatment and may be fatal. Discontinue drug in patients developing RPLS.
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Diarrhoea
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Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.
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Wound healing
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This treatment may impair wound healing and temporary interruption of treatment is recommended in patients undergoing major surgical procedures. Resume treatment based on clinical judgement of adequate wound healing.
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Baseline investigations
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Consider ECG and troponin at baseline. There is no clear evidence regarding the efficacy/value of baseline ECG or troponin in patients receiving immune checkpoint inhibitor therapy. Some cancer specialists obtain baseline testing, and others continue this through the initial period of therapy. Consider urinalysis at baseline, particularly in patients with additional risk factors for developing immune-related acute kidney injury.
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Blood tests
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FBC, EUC, eGFR, LFTs, serum cortisol, TFTs and BSL at baseline.
Repeat FBC, EUC, eGFR, LFTs and BSL prior to each cycle. Check TFTs every 4-6 weeks during the course of treatment and every 12 weeks after finalising the treatment. Consider checking serum cortisol every 4-6 weeks during the course of treatment and every 12 weeks after finalising the treatment. Check lipase and amylase if symptomatic of pancreatitis.
In the absence of suspicion of immune-related adverse events less frequent monitoring may be applicable, according to institutional guidelines. Evidence for the frequency of routine blood testing with immunotherapies varies within published studies and guidelines.
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Hepatitis and HIV
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Hepatitis screening is recommended in all patients who are to receive immune checkpoint inhibitors.
Immunotherapy is associated with inflammatory adverse reactions resulting from increased or excessive immune activity and patients are at risk of developing autoimmune hepatitis. It should be used with caution in patients who have a history of chronic hepatic infections (hepatitis B and C), detectable human immunodeficiency virus (HIV) viral load or acquired immune deficiency syndrome (AIDS).
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Vaccinations
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Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.
The safety of having vaccinations during immunotherapy is unknown. Patients in the clinical trials were typically allowed to receive inactivated and recombinant vaccines but not live vaccines.
Refer to the recommended schedule of vaccination for immunocompromised patients, as outlined in the Australian Immunisation Handbook.
Read more about COVID-19 vaccines and cancer.
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Effects of cancer treatment on fertility
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Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment.
Studies to evaluate the effects of immune checkpoint inhibitor therapy on fertility have not been performed. Therefore, the effect on male and female fertility is unknown. Limited evidence supports that immune checkpoint inhibitor-related hypogonadism due to orchitis and hypophysitis can impact fertility. Immune checkpoint inhibitors can cause fetal harm when given to pregnant women. A pregnancy test should be considered in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. There is very limited evidence to provide guidance regarding contraception timelines. Some studies have demonstrated PD-1 receptor occupancy for greater than 9 months after anti-PD-1 therapy (Brahmer et al., 2010). As a result, some cancer specialists advise using contraception for at least six months or even as long as two years after treatment finishes.
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