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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Emetogenicity moderate to high
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Routine antiemetic premedication may not be required for continuous dosing of some moderate to high emetic risk oral drugs. Consider if patient develops significant nausea or vomiting and reassess routinely. In clinical practice, the administration of oral metoclopramide may be sufficient to control nausea.
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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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Hypertension
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Patients treated with lenvatinib may experience an increased incidence of hypertension.
Pre-existing hypertension should be adequately controlled prior to commencing treatment and blood pressure should be monitored after 1 week of treatment, then every 3 weeks (prior to commencement of each cycle). Refer to dose modification section for management of hypertension.
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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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Diarrhoea
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Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.
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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 (e.g. prior surgery or radiation therapy). Patients should be monitored for signs and symptoms of GI perforation.
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Haemorrhage
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Serious and sometimes fatal haemorrhagic events have been reported with this treatment. Patients should be monitored for signs and symptoms of severe bleeding. Use with caution in patients with risk of bleeding (ie. coagulopathy, concurrent anticoagulant or antiplatelet medications etc.) In the case of bleeding, dose interruptions, adjustments or discontinuation of therapy may be necessary.
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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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Hepatotoxicity
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Severe hepatotoxicity (including fatal outcomes) has been observed with this treatment.
Monitor for abnormal liver function tests (LFTs), jaundice and tiredness. Refer to blood tests and dose modification sections for specific recommendations.
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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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Prolongation of QT interval
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This treatment may prolong the QT interval and increase the risk of cardiac arrhythmia. Use with caution in patients with a congenital long QT syndrome, patients treated with a high cumulative dose of anthracycline therapy, patients taking medications that may prolong the QT interval and those with electrolyte disturbances. Risk factors (e.g. electrolyte abnormalities) should be corrected, where possible, prior to commencement of treatment and the concurrent use of drugs that may prolong the QT interval should be avoided. Baseline and periodic monitoring of electrocardiogram (ECG) and electrolytes (potassium, magnesium, calcium) should be considered in patients at high risk of QT prolongation. Read more about drugs that may prolong QTc interval at crediblemeds.org (registration required).
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Proteinuria
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Proteinuria has been reported in patients treated with lenvatinib, usually occurring early in the course of the treatment.
Diabetes, high blood pressure and kidney disease are risk factors for developing proteinuria.
Monitor for proteinuria by urine dipstick analysis at baseline and regularly during treatment. If proteinuria is detected, consider 24-hour urinary protein determination. For those who develop moderate to severe proteinuria dose interruptions, adjustments, or discontinuation of treatment may be necessary.
Lenvatinib should be discontinued in the event of nephrotic syndrome.
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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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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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Wound healing
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Some suggest (Bose et al. 2010- see link to abstract) that antiangiogenic tyrosine kinase inhibitors (TKI's) be interrupted for at least one week (48 hours for agents with short half life) before surgery and not re-initiated until adequate wound healing has occurred. At many institutions, therapy with these agents is held for four weeks after major surgery and for at least two weeks after minor surgery, although there are no prospective data validating this approach. The decision to resume therapy following a major surgical intervention should be based upon clinical judgement of recovery from surgery.
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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, calcium, magnesium, phosphate, serum cortisol, TFTs, and BSL at baseline.
Repeat FBC, EUC, eGFR, calcium, magnesium, phosphate 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. Repeat LFTs every 3 weeks. 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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