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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Hypersensitivity/infusion related reaction
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High risk with etoposide and rituximab.
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Premedication
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The product information states that premedication is required for this treatment.
Note: a corticosteroid is included as part of this treatment and therefore additional corticosteroid may not be required as premedication.
Please refer to the treatment schedule for the suggested premedication regimen. This may be substituted to reflect institutional policy.
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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.
As this protocol includes a steroid, additional antiemetic steroids may not be required, despite the PBS approved combination of an NK1 receptor antagonist, 5HT3, and a steroid 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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Rituximab rapid infusion
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This regimen is not in line with the product monograph, however published literature indicates that it can be completed safely.
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Progressive multifocal leukoencephalopathy
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Use of monoclonal antibodies may be associated with an increased risk of progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal opportunistic viral infection of the brain. Patients must be monitored for any new or worsening neurological symptoms.
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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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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.
Note: an increased risk of cytarabine-induced neurotoxicity has been associated with kidney dysfunction.
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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 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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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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Constipation
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Prescribe prophylactic laxatives to prevent constipation related to the use of vinca alkaloids.
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Etoposide conversion factor
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Note: Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg.
Doses in this protocol are expressed as etoposide.
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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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Assess patient for risk of developing tumour lysis syndrome.
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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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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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Biosimilar drug
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Read more about biosimilar drugs on the Biosimilar Awareness Initiative page
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Blood tests
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FBC, EUC, eGFR, LFTs, LDH and BSL at baseline, prior to each treatment and regularly throughout treatment. 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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