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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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
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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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Thiopurine-S-methyltransferase (TPMT) enzyme deficiency
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Patients with an inherited deficiency of the TPMT enzyme are at an increased risk of, and prone to developing, rapid bone marrow depression which may lead to severe, life-threatening myelosuppression when undergoing treatment with thiopurines (azathioprine, mercaptopurine, tioguanine). This may be exacerbated by coadministration with drugs that inhibit TPMT, such as olsalazine, mesalazine or sulfasalazine.
Consider assessing thiopurine-S-methyltransferase (TPMT) activity prior to administration of thiopurines.
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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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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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SOS/VOD prevention
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Avoid hepatotoxic agents (e.g. azole antifungals) and conditioning regimens containing dual alkylating agents, thiotepa or both. Consider the use of prophylactic ursodeoxycholic acid (unlicensed indication).
Maintain aggressive clinical monitoring of fluid status, weight and LFTs. Institute early radiological investigation and commencement of required therapy.
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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 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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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, APTT, INR, fibrinogen, ATIII 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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