1. Home
  2. Medical oncology
  3. Urogenital
  4. Testicular

Testicular germ cell advanced or metastatic EP (etoposide ciSplatin)

This protocol was published over 10 years ago and has been assessed by the reference committee as suitable to be reviewed as required. The review due date has been removed. If something in this protocol requires reference committee consideration, please click on the feedback button at the bottom of the page.

Read more about the as required review process in this factsheet.

Clinicians are advised to consult with a medical oncologist from a tertiary treatment centre with high volume experience in testicular cancer prior to use of this regimen.

Link to ANZUP testicular cancer surveillance recommendations

Check for clinical trials in this patient group. Link to Australian Clinical Trials website

On this page
Expand all Collapse all Back to top

Cycle 1 to 4

Drug Dose Route Day
ciSplatin ^ 20 mg/m2 IV infusion 1 to 5
Etoposide ^* 100 mg/m2 IV infusion 1 to 5
Pegfilgrastim ** 6 mg Subcut 6

^ Dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of underdosing.

* Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

** the risk of neutropenia without G-CSF prophylaxis is ~ 10 to 20% and therefore may not be required.r However, in order to maintain dose intensity, many clinicians have chosen to give it as primary prophylaxis.

 

Frequency:
21 days 
Cycles:
4 
Notes:

Fertility issues including preservation (e.g. sperm banking) should be discussed with the patient prior to initiating chemotherapy

Drug status:

All drugs in this protocol are on the PBS general schedule

Pegfilgrastim is PBS authority

Cost:
~ $680 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 4

Day 1
Netupitant 300 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron 0.5 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy*
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2 and 3
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 4
Netupitant 300 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron 0.5 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 5
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 6
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food
Pegfilgrastim 6 mg (Subcut) Inject subcutaneously on day 6 at least 24 hours after chemotherapy**
Day 7 and 8
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food

  • Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide.

* The dose of dexamethasone on day 1 is 8 mg as per eviQ RC consensus but may be increased to 12 mg at the clinician’s discretion. Link to ID 7 Prevention of antineoplastic induced nausea and vomiting.

** The risk of neutropenia without G-CSF prophylaxis is ~ 10 to 20% and therefore may not be required.r However, in order to maintain dose intensity, many clinicians have chosen to give it as primary prophylaxis. 

Frequency:
21 days 
Cycles:
4 

Cycle 1 to 4

Drug Dose Route Day
ciSplatin ^ 20 mg/m2 IV infusion 1 to 5
Etoposide ^* 100 mg/m2 IV infusion 1 to 5
Pegfilgrastim ** 6 mg Subcut 6

^ Dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of underdosing.

* Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide

** the risk of neutropenia without G-CSF prophylaxis is ~ 10 to 20% and therefore may not be required.r However, in order to maintain dose intensity, many clinicians have chosen to give it as primary prophylaxis.

 

Frequency:
21 days 
Cycles:
4 
Notes:

Fertility issues including preservation (e.g. sperm banking) should be discussed with the patient prior to initiating chemotherapy

Drug status:

All drugs in this protocol are on the PBS general schedule

Pegfilgrastim is PBS authority

Cost:
~ $680 per cycle "How this cost is calculated"

The cost displayed on the protocol is intended as rudimentary guide only for the Australian context.

The cost includes anti-cancer drugs only (not antiemetics, supportive medications or consumables), unless otherwise indicated.

Drug unit costs are taken directly from the Pharmaceutical Benefits Scheme (PBS) website (www.pbs.gov.au). These costs are reviewed and updated on eviQ at 6 monthly intervals. Anti-cancer drugs that are not included on the PBS do not have a cost included in eviQ protocols.

Where there are differing unit costs based on vial sizes and tablet strengths, the mean unit cost is used. The cost of oral continuous therapy is based on a 28 day month.

Where oral drugs are available on the PBS for both 30- and 60-day prescriptions, the unit cost for the 30-day supply is used.

The protocol cost is derived from drug dose calculations based upon a default body surface area (BSA) of 1.8 m2; weight of 75 kg; and creatinine clearance of 75 mL/min.

One off loading doses and ongoing maintenance doses are not included in protocol cost calculations.

The cost displayed is the actual drug cost and does not necessarily reflect the cost incurred by the patient as many anti-cancer drugs are reimbursed on the PBS.

The supportive therapies (e.g. antiemetics, premedications, etc.), infusion times, diluents, volumes and routes of administration, if included, are listed as defaults. They may vary between institutions and can be substituted to reflect individual institutional policy.

Antiemetics if included in the treatment schedule are based upon recommendations from national and international guidelines. These are defaults only and may be substituted to reflect individual institutional policy. Select here for recommended doses of alternative antiemetics.

Cycle 1 to 4

Day 1
Netupitant 300 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron 0.5 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy*
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2 and 3
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 4
Netupitant 300 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with palonosetron)
Palonosetron 0.5 mg (PO) 60 minutes before chemotherapy (fixed dose preparation with netupitant)
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 5
Dexamethasone 8 mg (PO) 60 minutes before chemotherapy
ciSplatin 20 mg/m2 (IV infusion) in 1000 mL sodium chloride 0.9% over 60 minutes (dose should be calculated based on actual BSA, and should not be capped or modified, due to the risk of under dosing)
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 6
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food
Pegfilgrastim 6 mg (Subcut) Inject subcutaneously on day 6 at least 24 hours after chemotherapy**
Day 7 and 8
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food

  • Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg. Doses in this protocol are expressed as etoposide.

* The dose of dexamethasone on day 1 is 8 mg as per eviQ RC consensus but may be increased to 12 mg at the clinician’s discretion. Link to ID 7 Prevention of antineoplastic induced nausea and vomiting.

** The risk of neutropenia without G-CSF prophylaxis is ~ 10 to 20% and therefore may not be required.r However, in order to maintain dose intensity, many clinicians have chosen to give it as primary prophylaxis. 

Frequency:
21 days 
Cycles:
4 

Indications:

  • metastatic germ cell tumours (both non-seminoma and seminoma) where bleomycin is contraindicated
    • good prognosis tumours (by IGCCCG criteriar)

Exclusions:

  • intermediate or poor-prognosis (by IGCCCG criteria) metastatic germ cell tumours.
Venous access required

IV cannula (IVC) or central venous access device (CVAD) is required to administer this treatment.

Read more about central venous access device line selection
Hypersensitivity/infusion related reaction

High risk with etoposide.

Read more about Hypersensitivity reaction
Emetogenicity HIGH

Suggested default antiemetics have been added to the treatment schedule, and may be substituted to reflect institutional policy.

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.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Etoposide conversion factor

Note: Etopophos (etoposide phosphate) 113.6 mg is equivalent to etoposide 100 mg.
Doses in this protocol are expressed as etoposide.
Cisplatin dosing

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).

Read more about prevention and management of cisplatin induced nephrotoxicity.
Hydration

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.

Read more about cisplatin hydration regimens
Ototoxicity

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.

Read more about ototoxicity - tinnitus and hearing loss
Peripheral neuropathy

Assess prior to each treatment. If a patient experiences > grade 2 review by medical officer before commencing treatment as alternate regimen may be considered.

Read more about peripheral neuropathy

Link to chemotherapy-induced peripheral neuropathy screening tool
Tumour marker monitoring

AFP and ßhCG should be monitored regularly throughout treatment, at least once per cycle
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.  

Access the PBS website
Blood tests

FBC, EUC, eGFR, LFTs, calcium and magnesium at baseline and prior to each treatment.
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. 

Read more about hepatitis B screening and prophylaxis in cancer patients requiring cytotoxic and/or immunosuppressive therapy
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 and fathering a child

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and contraception timeframe should be discussed with all patients of reproductive potential.

Read more about the impact of cancer treatment on fertility
Evidence for dose modifications is limited, and the recommendations made on eviQ are intended as a guide only. They are generally conservative with an emphasis on safety. Any dose modification should be based on clinical judgement, and the individual patient’s situation including but not limited to treatment intent (curative vs palliative), the anti-cancer regimen (single versus combination therapy versus chemotherapy versus immunotherapy), biology of the cancer (site, size, mutations, metastases), other treatment related side effects, additional co-morbidities, performance status and patient preferences.Suggested dose modifications are based on clinical trial findings, product information, published guidelines and reference committee consensus . The dose reduction applies to each individual dose and not to the total number of days or duration of treatment cycle unless stated otherwise. Non-haematological gradings are based on Common Terminology Criteria for Adverse Events (CTCAE) unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Note: Delay and dose reductions are not recommended as the efficacy of this treatment may be greatly compromised - clinicians are advised to consult with a medical oncologist from a tertiary treatment centre with high volume experience in testicular cancer if dose delay or reduction due to toxicities or renal or hepatic dysfunction is being contemplated; an alternative treatment regimen may need to be considered.

The drug interactions shown below are not an exhaustive list. For a more comprehensive list and for detailed information on specific drug interactions and clinical management, please refer to the specific drug product information and the following key resources: 

For more information see References & Disclaimer.

Cisplatin
  Interaction Clinical management
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely
Ototoxic drugs (e.g. aminoglycosides, frusemide, NSAIDs) Additive ototoxicity Avoid combination or perform regular audiometric testing
Neurotoxic drugs (e.g. vincristine, paclitaxel) Additive neurotoxicity Monitor closely for neuropathy if combination used
Paclitaxel Administration schedule may influence the development of myelosuppression Minimise toxicity by administering paclitaxel first in regimens using the combination
Carbamazepine, phenytoin, valproate Decreased antiepileptic plasma levels Monitor antiepileptic serum levels and seizure frequency for efficacy; adjust dosage as appropriate or select alternative antiepileptic (e.g. clonazepam, diazepam, lorazepam)
Etoposide and Etoposide Phosphate
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, ciclosporin etc.) Increased toxicity of etoposide possible due to reduced clearance Avoid combination or monitor for etoposide toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of etoposide possible due to increased clearance Avoid combination or monitor for decreased clinical response to etoposide
Glucosamine Reduced efficacy of etoposide (due to induction of glucose-regulated stress proteins resulting in decreased expression of topoisomerase II) Avoid combination or monitor for decreased clinical response to etoposide
Grapefruit juice Reduced efficacy of oral etoposide possible due to possible alteration of P-gp mediated intestinal transport of etoposide Avoid combination or monitor for decreased clinical response to etoposide
NK-1 antagonist e.g. aprepitant, fosaprepitant, netupitant
  Interaction Clinical management
Dexamethasone Increased effects/toxicity of dexamethasone due to inhibition of its metabolism via CYP3A4

Reduce dose of antiemetic dexamethasone by approximately 50% when adding a NK-1 antagonist. For protocols that already recommend a NK-1 antagonist, the dose reduction of antiemetic dexamethasone has already been taken into account.

If dexamethasone is part of the chemotherapy protocol, dose reduction as per the product information is not routinely recommended in clinical practice and no additional dexamethasone is required for antiemetic cover. 
Warfarin

Reduced anticoagulant efficacy of warfarin due to increased clearance (aprepitant induces CYP2C9). *Note interaction only applicable to aprepitant/ fosaprepitant

INR should be monitored in the 2 week period, particularly at 7 to 10 days following the administration of aprepitant/ fosaprepitant
Combined oral contraceptive Reduced contraceptive efficacy due to increased clearance. *Note interaction only applicable to aprepitant/ fosaprepitant Alternative non-hormonal methods should be used during and for 1 month after stopping aprepitant/ fosaprepitant
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of NK-1 antagonist possible due to increased clearance Avoid combination or monitor for decreased antiemetic effect. Consider using an alternative antiemetic regimen
CYP3A4 inhibitors (e.g. azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of NK-1 antagonist possible due to reduced clearance Avoid combination or monitor for increased adverse effects of NK-1 antagonist (e.g. headache, hiccups, constipation)
Drugs metabolised by CYP3A4 (e.g. etoposide, imatinib, irinotecan, midazolam, paclitaxel, vinblastine, vincristine etc.) Increased effects/toxicity of these drugs possible due to inhibition of CYP3A4 by NK-1 antagonist Avoid combination or monitor for increased toxicity especially with orally administered drugs
General
  Interaction Clinical management
Warfarin Anti-cancer drugs may alter the anticoagulant effect of warfarin. Monitor INR regularly and adjust warfarin dosage as appropriate; consider alternative anticoagulant.
Direct oral anticoagulants (DOACs) e.g. apixaban, rivaroxaban, dabigatran

Interaction with both CYP3A4 and P-gp inhibitors /inducers.

DOAC and anti-cancer drug levels may both be altered, possibly leading to loss of efficacy or toxicity (i.e. increased bleeding).

Apixaban: avoid concurrent use with strong CYP3A4 and P‑gp inhibitors. If treating VTE, avoid use with strong CYP3A4 and P‑gp inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 and P‑gp  inhibitors.

Dabigatran: avoid combination with strong P‑gp inducers and inhibitors.

If concurrent use is unavoidable, monitor closely for efficacy/toxicity of both drugs.
Digoxin Anti-cancer drugs can damage the lining of the intestine; affecting the absorption of digoxin. Monitor digoxin serum levels; adjust digoxin dosage as appropriate.
Antiepileptics Both altered antiepileptic and anti-cancer drug levels may occur, possibly leading to loss of efficacy or toxicity. Where concurrent use of an enzyme-inducing antiepileptic cannot be avoided, monitor antiepileptic serum levels for toxicity, as well as seizure frequency for efficacy; adjust dosage as appropriate.
Also monitor closely for efficacy of the anti-cancer therapy.
Antiplatelet agents and NSAIDs Increased risk of bleeding due to treatment related thrombocytopenia. Avoid or minimise combination.
If combination deemed essential, (e.g. low dose aspirin for ischaemic heart disease) monitor for signs of bleeding.
Serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs e.g. paroxetine) and serotonin noradrenaline reuptake inhibitors (SNRIs e.g. venlafaxine) Increased risk of serotonin syndrome with concurrent use of 5-HT3 receptor antagonists (e.g. palonosetron, ondansetron, granisetron, tropisetron, dolasetron, etc.) Avoid combination.
If combination is clinically warranted, monitor for signs and symptoms of serotonin syndrome (e.g. confusion, agitation, tachycardia, hyperreflexia).
For more information link to TGA Medicines Safety Update
Vaccines Diminished response to vaccines and increased risk of infection with live vaccines. Live vaccines (e.g. BCG, MMR, zoster and varicella) are contraindicated in patients on immunosuppressive therapy. Use with caution in patients on non-immunosuppressive therapy.
For more information; refer to the recommended schedule of vaccination for cancer patients, as outlined in the Australian Immunisation Handbook

eviQ provides safe and effective instructions on how to administer cancer treatments. However, eviQ does not provide every treatment delivery option, and is unable to provide a comprehensive list of cancer treatment agents and their required IV line giving set/filter. There may be alternative methods of treatment administration, and alternative supportive treatments that are also appropriate. Please refer to the individual product information monographs via the TGA and Australian Injectable Drugs Handbook websites for further information.

Day 1 to 5

Approximate treatment time: 3.5 hours

General patient assessment prior to each day of treatment.

Peripheral neuropathy assessment tool.

Any toxicity greater than grade 2 should be reviewed by medical officer, however delay and dose reductions are not recommended as the efficacy of the treatment may be greatly compromised- clinicians are advised to consult with a medical oncologist from a tertiary treatment centre with high volume experience in testicular cancer if dose delay or reduction is being contemplated. An alternative treatment regimen may need to be considered.

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

Verify dexamethasone taken or administer as prescribed.

Cisplatin

Commence prehydration for cisplatin:
  • administer 10 mmol magnesium sulphate (MgSO4) in 1000 mL sodium chloride 0.9% over 60 minutes
  • ensure patient has passed urine prior to cisplatin administration as per institutional policy.
Administer cisplatin (irritant):
  • via IV infusion over 60 minutes
  • flush with 100 mL of sodium chloride 0.9%
  • observe for hypersensitivity reactions which can increase with the number of cycles administered and when given with concomitant radiation therapy. 
Infusion-related reaction (IRR):

Stop infusion at first sign of anaphylaxis or severe IRR and manage as per emergency. 

Etoposide

Administer etoposide (irritant):
  • via IV infusion over 30 to 60 minutes
    • if using etoposide phosphate administer in ~ 50 mL sodium chloride 0.9% or glucose 5% over ~15 minutes
  • flush with ~ 100 mL sodium chloride 0.9%.
Infusion-related reaction:

Stop infusion at first sign of anaphylaxis or severe IRR and manage as per emergency. 

  • if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate
  • for severe reactions seek medical assistance immediately and do not restart infusion.
Potential adverse events:
  • rapid infusion may cause hypotension.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Note: ensure arrangements have been made for the administration of growth factor on day 6 (24 hours post day 5 chemotherapy).

Continue safe handling precautions until 7 days after completion of drug(s).

Discharge information

Antiemetics - as/if prescribed.

Growth factor support - as/if prescribed, and arrangements for administration.

Patient information

Ensure patient receives protocol patient information sheet.

The side effects listed below are not a complete list of all possible side effects for this treatment. Side effects are categorised into the approximate onset of presentation and should only be used as a guide.

Immediate (onset hours to days)
Hypersensitivity reaction

Anaphylaxis and infusion related reactions can occur with this treatment.

Read more about hypersensitivity reaction 
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Taste and smell alteration

Read more about taste and smell changes
Bone pain

Bone pain, usually in the lower back or pelvis, associated with G-CSF.

Early (onset days to weeks)
Neutropenia

Abnormally low levels of neutrophils in the blood. This increases the risk of infection. Any fever or suspicion of infection should be investigated immediately and managed aggressively. 

Read more about immediate management of neutropenic fever
Thrombocytopenia

A reduction in the normal levels of functional platelets, increasing the risk of abnormal bleeding.  

Read more about thrombocytopenia
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following anti-cancer treatment, radiation therapy to the head, neck or oesophagus, and high-dose chemotherapy followed by a blood and marrow transplant (BMT).

Read more about oral mucositis and stomatitis
Diarrhoea

Read more about treatment induced diarrhoea
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Fatigue

Read more about fatigue
Peripheral neuropathy

Typically symmetrical sensory neuropathy, affecting the fingers and toes, sometimes progressing to the hands and feet.  It is associated with several classes of anti-cancer drugs. These include taxanes, platinum-based compounds, vinca alkaloids and some drugs used to treat multiple myeloma.

Read more about peripheral neuropathy
Nephrotoxicity

Kidney dysfunction resulting from damage to the glomeruli, tubules or renal vasculature.
Ototoxicity

Tinnitus and hearing loss may occur due to damage in the inner ear. Tinnitus is usually reversible, while hearing loss is generally irreversible. Hearing loss is dose-related, cumulative and may be worse in those with pre-existing hearing problems.

Read more about ototoxicity - tinnitus and hearing loss
Hypomagnesaemia, hypokalaemia, hypocalcaemia

Abnormally low levels of magnesium, potassium and calcium in the blood.

Late (onset weeks to months)
Anaemia

Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. 

Read more about anaemia
Alopecia

Hair loss may occur from all parts of the body. Patients can also experience mild to moderate discomfort of the hair follicles, and rarely pain as the hair is falling out.

Read more about alopecia and scalp cooling
Cardiotoxicity

Elevated risk of cardiovascular toxicity and metabolic syndrome.

Read more about cardiotoxicity associated with anti-cancer drugs.

Non-seminoma

The evidence supporting this protocol comes from a French multicentre randomised trial involving 257 patients comparing 3 cycles of BEP with 4 cycles of EP in patients with good risk nonseminomatous germ cell cancer defined according to the Institut Gustave Roussy prognostic model.r

Between October 1993 and May 1999 124 patients were randomised to receive three cycles of BEP (bleomycin 30 international units on days 1,8,15, etoposide 100mg/m2 days 1-5, cisplatin 20mg/m2 days 1-5) and 122 patients four cycles of EP (etoposide 100mg/m2 days 1-5, cisplatin 20mg/m2 days 1-5) every three weeks. The primary end point was equivalence.

Seminoma

Another prospective non-randomised multicentre study assessed the efficacy of EP in good prognosis advanced seminoma and the efficacy of VIP in intermediate or poor prognosis advanced seminoma.r Patients were stratified according to the International Germ Cell Cancer Collaboration Group (IGGCCG)r and the Medical Research Council. Between December 1999 and September 2008, 132 patients were accrued from 12 French centres. 108 good prognosis patients received EP (etoposide 100mg/m2 days 1-5, cisplatin 20mg/m2 days 1-5) and 24 intermediate /poor prognosis patients received VIP (etoposide 100mg/m2 days 1-5, ifosfamide 1.2g/m2, cisplatin 20mg/m2 days 1-5) with GCSF support. No formal hypothesis regarding response or survival was initially put forward.

Efficacy

The French study for nonseminomatous germ cell tumours demonstrated similar favourable response rates for 3 cycles of BEP or 4 cycles of EP, but a non-significant trend to worse survival for 3 cycles of BEP. It was not powered to assess survival. The recommendation is to use EP only in selected cases where BEP is contraindicated because of concerns about bleomycin toxicity.

GETUG T93BP Culine et alr

© Ann Oncol 2007

Progression-free survival and overall survivalr

© European Urology 2014

Toxicity

The toxicity of the two regimens is fairly similar, with the difference being pulmonary toxicity, grade 3-4 neutropaenia and peripheral neuropathy is worse with EP compared with BEP.r

© Annals of Oncology 2007

VIP was associated with more haematological toxicity including neutropenic fever (23% vs 12%) and one death due to septic shock. More patients received their planned four cycles of EP (n=104; 97%) than VIP (n=21; 88%).r

© European Urology 2014

[%id%]
[%title%]
[%abstract%]

Flinders Filters has partnered with eviQ to build reliable, robust search filters to retrieve core high level evidence on topics of significance to eviQ. The project goal is the provision of a sustainable model for evidence retrieval to ensure ongoing currency of content.

These search filters have been developed to retrieve the most up to date evidence from PubMed, in real time, using specifically designed search filters built to meet our needs.

Searches can be used when a protocol is scheduled for review or at any time you choose. Please click on the Specific, Balanced and Sensitive tabs below to access the Pubmed searches.

Specific Balanced Sensitive
restricted to retrieving randomised control trials and systematic reviews.

is the middle ground between sensitive and specific searches.

retrieves all clinically relevant evidence - generally a broader search on a given topic.

Access Flinders Filters, a division of the Flinders Digital Health Research Centre at Flinders University to read more about research solutions to searching problems.

Troubleshooting

Occasionally the searches may not display correctly or take too long to load (and will eventually timeout). This may be caused by Internet Explorer being unable to handle long URL's. You can rectify this by using Firefox, Safari or Google chrome. It is always a good idea to clear the cache regularly to ensure you are getting the most up to date search.

Feedback

If you identify any new articles that you believe should be included in the content, please use the feedback button below to inform us of the name of the article(s). 

Version 8

Date Summary of changes
12/03/2024

Protocol assessed by eviQ medical oncology reference committee and deemed suitable to be reviewed as required. Flag added, review date removed and version number increased to V.8. Read more about as required review protocol status in this factsheet.
18/07/2024 Late onset cardiotoxicity side effect block added to the protocol and patient information, approved at medical oncology reference committee meeting 24th May 2024. 

Version 7

Date Summary of changes
27/07/2023

Protocol updated with ADDIKD guideline recommendations. 

PDF of previous protocol.

Version number changed to V.7.
12/12/2023 "Non-PBS" footnote for netupitant and palonosetron removed from detailed treatment schedule.

Version 6

Date Summary of changes
18/11/2021 Cisplatin changed from moderately to highly emetogenic as per NCCN, MASCC/ESMO and ASCO guidelines and medical oncology reference committee consensus. Treatment schedule antiemetics and clinical information updated to reflect the change. NK-1 antagonist added to interactions. Version number changed to V.6.

Version 5

Date Summary of changes
04/09/2020 Biosimilar drug added to clinical information. Version number changed to V.5.

Version 4

Date Summary of changes
04/05/2020 Clinical information updated- FBC nadir cycle 1 removed from blood tests. Approximate treatment time changed to 3.5 hours. Version number changed to V.4.
30/06/2020 Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Review 5 years.

Version 3

Date Summary of changes
08/10/2019 Clinical information updated with PBS expanded indications for GCSF. Treatment schedule note updated.

Version 2

Date Summary of changes
09/05/2014 Taken to medical oncology reference committee.
22/06/2014 Approved and published on eviQ. Review in one year.
27/03/2015 Reviewed by Medical Oncology Reference Committee. Links to Germ Cell Tumour HPCT protocols added. Review 2 years.
31/03/2017 Protocol discussed and decided to have a 5 year review period. Next due for review in 2020.
31/05/2017 Transferred to new eviQ website. Protocol version number changed to V.2.
22/06/2018 Antiemetics updated to be in line with international guidelines. Note to dexamethasone added.
25/03/2019 ANZUP surveillance recommendations added as related page. 

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

Send feedback for this page

First approved:
Last reviewed:
Review due:
As required

The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/1617

11 Oct 2024