Safety alert vincristine administration
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For safe administration of vincristine refer to the safety alert issued by the Australian Commission on Safety and Quality in Health Care
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Venous access
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Central venous access device (CVAD) is required to administer this treatment.
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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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Antiemetics for multi-day protocols
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Patients being treated with multi-day anticancer protocols should receive antiemetics tailored to the emetogenic risk of the drugs administered each day during treatment and for two days after completion of the anticancer protocol.
No standard antiemetic regimen exists for multi-day anticancer protocols. A combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies.
Ensure that patients also have sufficient antiemetics for breakthrough emesis:
Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR
Prochlorperazine 10 mg PO every 6 hours when necessary.
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Cumulative lifetime dose of anthracyclines
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Cumulative doses should take into account all previous anthracyclines received during a patient’s lifetime (i.e. daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone).
Criteria for reducing the total anthracycline cumulative lifetime dose include:
- patient is elderly
- prior mediastinal radiation
- hypertensive cardiomegaly
- concurrent therapy with high dose cyclophosphamide and some other cytotoxic drugs (e.g. bleomycin, dacarbazine, dactinomycin, etoposide, melphalan, mitomycin and vincristine).
Baseline clinical assessments include echocardiogram (ECHO) or gated heart pool scan (GHPS) and electrocardiogram (ECG) evaluation.
Patients with normal baseline cardiac function (left ventricular ejection fraction (LVEF) > 50%) and low risk patients require LVEF monitoring when greater than 70% of the anthracycline threshold is reached or if the patient displays symptoms of cardiac impairment. Post-treatment cardiac monitoring is recommended for patients who have received high levels of total cumulative doses of anthracyclines at the clinician's discretion.
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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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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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Administration details
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Long-term suppression of gastric secretions may decrease the absorption of some tyrosine kinase inhibitors (TKIs). Patients should avoid taking H2-receptor antagonists or proton-pump inhibitors while undergoing therapy with this TKI. Antacids may be used instead, but should be avoided within 2 hours of the TKI dose.
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Pulmonary complications
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Clinicians should evaluate patients for signs and symptoms of underlying cardiopulmonary disease before starting treatment and during treatment.
Pleural effusions are dose dependent events and dose interruption, reduction or steroids should be considered. They are more common with dasatinib than with imatinib and may be bilateral or unilateral. Up to 35 % of patients treated with dasatinib on phase I/II studies developed pleural effusions, most often exudative.
Pulmonary arterial hypertension (PAH) is an uncommon but serious complication. Echocardiogram is recommended in symptomatic patients (i.e. dyspnoea, cough, fatigue) and those with pleural effusions. Dasatinib should be withheld during evaluation if symptoms are severe, and permanently discontinued if PAH is confirmed i.e. not rechallenged.
Pneumonitis and interstitial lung disease has also been reported.
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Fluid retention/oedema
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Dasatinib may cause severe fluid retention, including pleural and pericardial effusions, severe ascites, severe pulmonary oedema, and generalised oedema. This may be dose-related.
Risk increases in patients greater than 65 years, patients with hypertension or prior cardiac history and those treated with twice daily dosing. (Note: once daily dosing is the recommended dosing schedule for all phases).
Monitor regularly for signs and symptoms of fluid retention. Chest x-ray is recommended for symptoms suggestive of pleural effusion (eg. cough, dyspnoea).
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Gastrointestinal toxicity
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Diarrhoea is a common side effect of tyrosine kinase inhibitors (TKI) (e.g imatinib and dasatinib). If severe diarrhoea occurs, discontinue TKI until condition improves or resolves.
Constipation has also been commonly reported with these regimens possibly related to the use of vinca alkaloids.
Patients should be monitored closely, and prophylactic or symptom control anti-diarrhoeal/laxatives prescribed accordingly.
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Haemorrhagic cystitis associated with high dose chemotherapy
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Hydration regimen pre high dose cyclophosphamide or ifosfamide (as per local guidelines).
There is limited evidence and no consensus regarding hydration regimens and mesna dose, route or timing of administration.
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Efficacy of therapy
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Measure efficacy of therapy using a standardised RT-PCR assay for BCR-ABL transcripts. Assess after the first cycle, at 2 to 4 month intervals while on hyper CVAD, and at 4 to 6 month intervals thereafter. Alternate therapies should be considered for patients who do not achieve a major molecular remission (defined as BCR-ABL less than 0.1% in the marrow) by 3 months and for those who lose their initial response on serial monitoring.
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Corticosteroids
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Diabetic patients should monitor their blood glucose levels closely. To minimise gastric irritation, advise patient to take immediately after food. Consider the use of a H2 antagonist or proton pump inhibitor if appropriate.
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Peripheral neuropathy
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Assess prior to each treatment. Based on clinical findings, temporary omission, dose reduction or cessation of the vinca alkaloid may be indicated; review by medical officer before commencing treatment.
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Mesna dosing and administration
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There is evidence supporting variations in mesna doses and administration timings, with no clear evidence that one particular regimen is superior to another. The eviQ mesna recommendations may be based upon the individual trial/study or reference committee consensus and provide guidance on one safe way to administer the protocol. Individual institutional policy may vary and should be evidence-based.
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Tumour lysis risk
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Patients are at high risk of developing tumour lysis syndrome, prophylaxis is recommended.
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Pneumocystis jirovecii pneumonia (PJP) prophylaxis
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PJP prophylaxis is recommended e.g. trimethoprim/sulfamethoxazole 160/800 mg PO one tablet twice daily, twice weekly (e.g. on Mondays and Thursdays) OR one tablet three times weekly (e.g. on Mondays, Wednesdays and Fridays).
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Antiviral prophylaxis
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Antiviral prophylaxis is recommended.
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Antifungal prophylaxis
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Antifungal prophylaxis is recommended.
Note: Extended spectrum azole antifungals (e.g. posaconazole, voriconazole and itraconazole) should be avoided with vinca alkaloids. Metabolism is inhibited by azoles and neurotoxicity can be potentiated.
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Biosimilar drug
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Read more about biosimilar drugs on the Biosimilar Awareness Initiative page
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Growth factor support
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G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.
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Blood tests
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FBC, EUC, eGFR, LFTs, LDH, calcium, magnesium and phosphate at baseline and prior to each cycle. TSH and BSL at baseline and regularly throughout treatment as clinically indicated.
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Hepatitis B screening and prophylaxis
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Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.
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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.
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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Fertility, pregnancy and lactation
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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. There is a risk of foetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. Pregnancy must be avoided while a female patient is on tyrosine kinase inhibitor (TKI) therapy. There are very few reports of pregnancy outcomes in partners of men receiving second or third-generation TKIs. Although the majority of infants fathered by men taking dasatinib were reported to be without congenital disabilities at birth, the general advice is for couples to avoid pregnancy (Carlier et al., 2017; Cortes et al., 2015). The safety of these drugs has not been proven, and therefore, pregnancy should be avoided. Effective contraception methods and adequate contraception timeframes should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.
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