Venous access
|
Central venous access device (CVAD) is required to administer this treatment.
|
Hypersensitivity/infusion related reaction
|
High risk with etoposide.
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.
|
Antiemetics for multi-day protocols
|
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.
|
Pre-hydration
|
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.
|
Methotrexate dosing and monitoring
|
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.
|
Methotrexate interactions
|
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.
|
Pegaspargase
|
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.
|
Pancreatitis
|
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.
|
Thrombotic events
|
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 then periodically monitored during and after treatment according to local policy.
Patients should be on thromboprophylaxis with enoxaparin to prevent thrombotic events unless contraindicated. Serious thrombotic events may occur in patients receiving pegaspargase; in the event of CNS thrombosis, discontinuation of pegaspargase should be strongly considered. Read more about Management of asparaginase therapy
|
Hepatotoxicity
|
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.
|
Ifosfamide-induced encephalopathy
|
May occur in patients treated with high dose ifosfamide (~ 5 to 8 g/m2). Assess neurological function prior to each ifosfamide dose.
|
Haemorrhagic cystitis associated with high dose chemotherapy
|
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.
|
Mesna dosing and administration
|
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.
|
Etoposide conversion factor
|
Doses in this protocol are expressed as etoposide. Note: Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg.
Etoposide phosphate is the preferred formulation for this protocol, as solutions of conventional etoposide would exceed the maximum concentration of 0.4 mg/mL and may precipitate. All administration details in this protocol refer to etopophos.
|
Corticosteroids
|
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.
|
Central nervous system (CNS) prophylaxis
|
Consider CNS relapse assessment in patients with high grade lymphoma.
|
Tumour lysis risk
|
Assess patient for risk of developing tumour lysis syndrome.
|
Pneumocystis jirovecii pneumonia (PJP) prophylaxis
|
PJP prophylaxis is recommended.
Myelosuppression may be exacerbated if trimethoprim/sulfamethoxazole is used in combination with methotrexate.
|
Antiviral prophylaxis
|
|
Antifungal prophylaxis
|
|
Biosimilar drug
|
Read more about biosimilar drugs on the Biosimilar Awareness Initiative page
|
Growth factor support
|
G-CSF (short or long-acting) is available on the PBS for chemotherapy induced neutropenia depending on clinical indication and/or febrile neutropenia risk.
|
Blood product support
|
The use of FFP and cryoprecipitate may be required to maintain fibrinogen levels to a normal range.
|
Blood tests
|
FBC, EUC, eGFR, BSL, LDH, uric acid, albumin, triglycerides and total cholesterol levels at baseline and prior to each cycle. LFTs, bilirubin, lipase, amylase, APTT, PT, INR, fibrinogen, antithrombin III levels at baseline and at least once or twice a week as clinically indicated.
Monitor methotrexate levels every 24 hours until the level is less than 0.1 micromol/L.
|
Hepatitis B screening and prophylaxis
|
Routine screening for HBsAg and anti-HBc is recommended prior to initiation of treatment. Prophylaxis should be determined according to individual institutional policy.
|
Vaccinations
|
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.
|
Fertility, pregnancy and lactation
|
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.
|