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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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Antiemetic therapy should be administered throughout the duration of the chemotherapy protocol and to cover delayed nausea. The acute and delayed emetic risk of multi-day chemotherapy protocols will overlap depending on the individual drugs and their sequence of administration. More or less antiemetic cover may be required.
As a steroid has been included as part of this protocol, additional antiemetic steroids are not required.
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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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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Pre-hydration
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Pre-hydration with sodium bicarbonate 8.4% infusion. Urinary pH must be greater than 7 prior to commencing methotrexate infusion.
Consider prescribing sodium bicarbonate oral capsules for administration prior to methotrexate infusion.
Sodium bicarbonate 8.4% should continue until the methotrexate level is equal to or less than 0.1 micromol/L.
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Ocular toxicities
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Administer corticosteroid eye drops to minimise corneal toxicity from high dose cytarabine. Commence on the day of first dose of cytarabine and continue for at least 72 hours after completion of final cytarabine dose.
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Cytarabine induced neurotoxicity
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This may occur in patients treated with high dose cytarabine. Assess cerebellar function prior to each cytarabine dose.
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Cytarabine syndrome
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Treatment with cytarabine may cause a "cytarabine syndrome" characterised by flu-like symptoms, skin rash and occasionally chest pain.
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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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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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Diarrhoea
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Consider prescribing prophylactic anti-diarrhoeal (e.g. loperamide) to prevent treatment induced diarrhoea.
If severe diarrhoea occurs, discontinue dasatinib until condition improves or resolves.
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High dose methotrexate
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Monitoring of methotrexate levels is essential as delayed methotrexate excretion is potentially an emergency situation. Methotrexate levels to be monitored every 24 hours until level is less than 0.1 micromol/L.
Methotrexate is renally eliminated. Renal function must be evaluated prior to treatment.
Methotrexate exits slowly from third space compartments (e.g. pleural effusions or ascites), resulting in a prolonged terminal plasma half-life and unexpected toxicity. In patients with significant third space accumulations, it is advisable to evacuate the fluid before treatment and to monitor plasma methotrexate levels.
Glucarpidase is recommended in patients with high dose methotrexate (HDMTX)-induced acute kidney injury and delayed methotrexate clearance. It can rapidly lower methotrexate levels and early administration within 48 to 60 hours from the start of the HDMTX infusion is critical, as life-threatening toxicities may not be preventable beyond this time point.r
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Methotrexate interactions
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Avoid administering the following drugs in combination with high dose methotrexate: ciprofloxacin, NSAIDs, probenecid, proton pump inhibitors (PPIs) (e.g. esomeprazole, omeprazole, pantoprazole), sulphonamides (e.g. sulfamethoxazole (in Bactrim®, Septrin®)), penicillins (e.g. piperacillin (in Tazocin®)) and trimethoprim. Severe mucositis may occur if administered together.
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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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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.
Myelosuppression may be exacerbated if trimethoprim/sulfamethoxazole is used in combination with methotrexate.
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Antifungal prophylaxis
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Antifungal prophylaxis is recommended. e.g. posaconazole 300 mg PO twice daily for one day then 300 mg PO daily.
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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, 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.
Methotrexate levels to be monitored every 24 hours until level is less than 0.1 micromol/L.
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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. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.
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