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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Premedication
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Original pemetrexed trials included hydroxocobalamin and folic acid to commence 5 to 7 days prior to the first cycle of chemotherapy, however the PEMVITASTART (Singh et al 2019) trial has demonstrated that concurrent administration does not lead to increased haematological toxicity. It is the opinion of the reference committee that hydroxocobalamin and folic acid may be administered 5 to 7 days prior to, or simultaneously with, cycle 1 of pemetrexed based chemotherapy.
Hydroxocobalamin (Vit B12) 1000 micrograms intramuscularly and repeat once every 3 cycles;
Folic acid 500 micrograms PO once daily continuously until 21 days after the last dose of pemetrexed.
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Emetogenicity HIGH
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Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.
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.
A steroid has been included both as an antiemetic and premedication for hypersensitivity in this protocol.
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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Cisplatin dosing
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Directly measured glomerular filtration rate (mGFR) is preferred for initial dosing when eGFR < 60 mL/min/1.73 m2, especially when cisplatin dose > 50 mg/m2 or when eGFR is unreliable (e.g., extremes of body composition, amputees, paraplegia).
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Hydration
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Hydration helps to prevent cisplatin-induced nephrotoxicity.
The default regimen is appropriate for patients with normal electrolytes, kidney function, fluid status etc. and should be adjusted according to individual requirements.
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Ototoxicity
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Ototoxicity may occur with platinum-based therapy; patients should be monitored for signs and symptoms. Platinum compounds should be used with caution in patients with pre-existing conditions or risk factors.
Ototoxicity may become more severe in patients being treated with other drugs with nephrotoxic potential e.g. aminoglycosides.
An audiometry test should be performed if symptoms develop.
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Peripheral neuropathy
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Assess prior to each treatment. If a patient experiences grade 2 or greater peripheral neuropathy, a dose reduction, delay, or omission of treatment may be required; review by medical officer before commencing treatment.
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Gastrointestinal perforation
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Bevacizumab has been associated with serious cases of gastrointestinal (GI) perforation and should be permanently discontinued in patients who develop it.
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Haemorrhage
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Patients treated with bevacizumab have an increased risk of haemorrhage, especially tumour associated haemorrhage and minor mucocutaneous haemorrhage (e.g. epistaxis). Bevacizumab should be used with caution in patients at risk of bleeding.
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Hypertension
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Pre-existing hypertension should be adequately controlled prior to commencing bevacizumab and blood pressure should be monitored during therapy. Commence or adjust antihypertensive medication as clinically indicated.
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Proteinuria
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Patients may be at increased risk of developing proteinuria when treated with bevacizumab. Baseline urinalysis for proteinuria is recommended prior to commencement of therapy, and as clinically indicated. Routine testing prior to each treatment is no longer recommended, as dose reductions for low/intermediate levels of proteinuria are not recommended.
Clinicians are advised to consider evaluating for proteinuria periodically (e.g. every 3 to 4 months) or in patients with clinical concerns (e.g. oedema/unexplained hypoalbuminemia) as treatment interruption may be required if proteinuria is significant (e.g. > 3 g/L).
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Reversible posterior leukoencephalopathy syndrome (RPLS)
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Bevacizumab should be discontinued in patients who develop reversible posterior leukoencephalopathy syndrome (RPLS). The risk of reinitiating bevacizumab therapy in patients previously experiencing RPLS is not known.
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Thromboembolism
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Both arterial and venous thromboembolic events have been observed in patients with this treatment.
Therefore, use with caution in patients at increased risk or with a history of thrombotic events (i.e., cerebrovascular and cardiovascular disease)
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Wound healing
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Bevacizumab may adversely affect wound healing and should not be initiated in patients with a serious non-healing wound or ulcer. Bevacizumab should be withheld at least 28 days prior to elective surgery. Bevacizumab can be restarted 28 days after surgery provided wound healing is complete.
Necrotising fasciitis, including fatal cases, has rarely been reported in patients treated with bevacizumab; usually secondary to wound healing complications, gastrointestinal perforation or fistula formation. Bevacizumab therapy should be discontinued in patients who develop necrotising fasciitis, and appropriate treatment should be promptly initiated.
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Third space effusion
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Consider draining large third space effusions prior to pemetrexed treatment to avoid prolonged exposure.
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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, calcium, magnesium and phosphate at baseline and prior to each treatment.
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Hepatitis B screening and prophylaxis
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Routine screening for HBsAg and anti-HBc is NOT usually recommended for patients receiving this treatment.
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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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