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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Hypersensitivity/infusion related reaction
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High risk with pegaspargase.
Hypersensitivity reactions may occur, e.g. life-threatening anaphylaxis, particularly in patients with known hypersensitivity to the other forms of asparaginase. Adequate medical treatment and provisions should be available for immediate use in the event of an anaphylactic reaction. Patients that develop hypersensitivity to the E. coli derived formulation may be able to switch to Erwinia asparaginase.
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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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Pegaspargase
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Pegaspargase is associated with numerous toxicities including hypersensitivity, hepatotoxicity, coagulation abnormalities, pancreatitis, hyperlipidaemia, hyperglycaemia and CNS effects. Therefore routine monitoring and assessment of several parameters are required throughout treatment.
For comprehensive information on formulations, dosing, interactions, adverse reactions and specific monitoring parameters for asparaginase, see Management of asparaginase therapy document.
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Pancreatitis
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Pancreatitis (both haemorrhagic or necrotising) has been reported in patients receiving pegaspargase with fatal outcomes. If pancreatitis is suspected pegaspargase should be discontinued and not restarted if confirmed. Serum amylase and/or lipase measurements should be performed frequently to identify early signs of pancreatic inflammation. If treatment is discontinued due to pancreatitis, appropriate investigations (e.g. ultrasound) should be performed at least four months following termination of therapy.
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Hepatotoxicity
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Caution is required when pegaspargase is given in combination with other hepatotoxic substances. If pegaspargase is given in combination with hepatotoxic substances, the patient should be closely monitored for liver impairment, especially if there is pre-existing hepatic impairment.
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Thrombotic events
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Serious thrombotic events may occur in patients receiving pegaspargase and should be discontinued if they occur. Increased prothrombin time (PT), increased activated partial thromboplastin time (APTT), and hypofibrinogenaemia may occur in patients receiving pegaspargase. A baseline coagulation profile (including antithrombin III) should be established and periodically monitored during and after treatment.
Patients should be on thromboprophylaxis with enoxaparin to prevent thrombotic events unless contraindicated.
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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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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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Constipation
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Prescribe prophylactic laxatives to prevent constipation related to the use of vinca alkaloids.
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Methotrexate dosing and monitoring
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Directly measured GFR is preferred for initial dosing when eGFR < 60 mL/min/1.73 m2, especially when methotrexate dose ≥ 500 mg/m2 or when eGFR is unreliable (e.g., extremes of body composition, amputees, paraplegia).
Monitor kidney function before, during and after methotrexate administration to identify signs of kidney function deterioration. 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 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.
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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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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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Methotrexate toxicity
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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
Read more about high dose methotrexate-induced toxicity.
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Ifosfamide-induced encephalopathy
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May occur in patients treated with high dose ifosfamide (~ 5 to 8 g/m2). Assess neurological function prior to each ifosfamide dose.
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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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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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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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Antiviral prophylaxis
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Antiviral prophylaxis is recommended.
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Antifungal prophylaxis
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Antifungal prophylaxis is recommended e.g. AmBisome 50 mg IV ONCE daily three times weekly (e.g. on Mondays, Wednesdays and Fridays) or fluconazole 200 mg to 400 mg PO daily.
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 product support
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The use of FFP and cryoprecipitate may be required to maintain fibrinogen levels to a normal range.
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Blood tests
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FBC, EUC, eGFR, LFTs, LDH, bilirubin, albumin, uric acid, lipase, amylase at baseline and twice a week or more frequent 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. 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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