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Small cell lung cancer extensive disease cARBOplatin etoposide and durvalumab

This protocol is not exportable and does not have a calculator.

Treatment must be initiated and supervised by specialist physicians experienced in the treatment of cancer using immunological agents. Before commencing immunotherapy treatment in any patient, clinicians should have an understanding of the immune-related adverse events (irAEs) associated with immunotherapy treatment and their management.

Check for clinical trials in this patient group. Link to Australian Clinical Trials opens in a new tab or window website

Link to Clinical practice guidelines for the treatment of lung cancer opens in a new tab or window

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Cycle 1 to 4

Drug Dose Route Day
Durvalumab 1,500 mg IV infusion 1
cARBOplatin 5 AUC * IV infusion 1
Etoposide ** 100 mg/m2 IV infusion 1 to 3

*If estimated GFR is greater than 125 mL/min (i.e. 5 AUC doses greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

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

Frequency:
21 days
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Cycle 5 and further cycles

Drug Dose Route Day
Durvalumab 1,500 mg IV infusion 1
Frequency:
28 days 
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity
Notes:

The CASPIANr and KEYNOTE-604 r studies permitted either carboplatin or cisplatin as the chemotherapy backbone. For selected patients it may be appropriate to substitute carboplatin with cisplatin.

Oral etoposide may be substituted for intravenous etoposide at the correct conversion dose. There is no evidence to support this but clinical circumstances may justify the use of oral etoposide in this regimen and in this patient population.

The standard oral etoposide dose is approximately twice the effective intravenous etoposide dose i.e. 200 mg/m2 (orally) = 100 mg/m2 (intravenously). Prediction of oral doses based on intravenous doses may be unreliable; it is recommended to titrate the oral dose to achieve maximal effect and minimise toxicity.

In the first few months after the start of immunotherapy, some patients can experience transient tumour flare (termed "pseudo progression" or an immune response). This may manifest as growth of existing lesions or the development of new lesions prior to later tumour regression. While this is rare (~5%), continuing treatment and performing a second scan 4 to 6 weeks later to confirm progression may be considered, particularly if the patient remains well.

Radiation recall has been observed with PD-L1 inhibitors, consideration should be given to the timing when starting this treatment after a prolonged course of radiation therapy

Drug status:

Carboplatin and etoposide are on the PBS general schedule opens in a new tab or window

Durvalumab is PBS authority opens in a new tab or window 

Cost:
~ $11,270 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, growth factor support 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
Durvalumab 1,500 mg (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes
cARBOplatin 5 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is greater than 125 mL/min (i.e. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
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) ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinician's discretion **
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes *

Frequency:
21 days
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Cycle 5 and further cycles

Day 1
Durvalumab 1,500 mg (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

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

**Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
28 days 
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Cycle 1 to 4

Drug Dose Route Day
Durvalumab 1,500 mg IV infusion 1
cARBOplatin 5 AUC * IV infusion 1
Etoposide ** 100 mg/m2 IV infusion 1 to 3

*If estimated GFR is greater than 125 mL/min (i.e. 5 AUC doses greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended

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

Frequency:
21 days
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Cycle 5 and further cycles

Drug Dose Route Day
Durvalumab 1,500 mg IV infusion 1
Frequency:
28 days 
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity
Notes:

The CASPIANr and KEYNOTE-604 r studies permitted either carboplatin or cisplatin as the chemotherapy backbone. For selected patients it may be appropriate to substitute carboplatin with cisplatin.

Oral etoposide may be substituted for intravenous etoposide at the correct conversion dose. There is no evidence to support this but clinical circumstances may justify the use of oral etoposide in this regimen and in this patient population.

The standard oral etoposide dose is approximately twice the effective intravenous etoposide dose i.e. 200 mg/m2 (orally) = 100 mg/m2 (intravenously). Prediction of oral doses based on intravenous doses may be unreliable; it is recommended to titrate the oral dose to achieve maximal effect and minimise toxicity.

In the first few months after the start of immunotherapy, some patients can experience transient tumour flare (termed "pseudo progression" or an immune response). This may manifest as growth of existing lesions or the development of new lesions prior to later tumour regression. While this is rare (~5%), continuing treatment and performing a second scan 4 to 6 weeks later to confirm progression may be considered, particularly if the patient remains well.

Radiation recall has been observed with PD-L1 inhibitors, consideration should be given to the timing when starting this treatment after a prolonged course of radiation therapy

Drug status:

Carboplatin and etoposide are on the PBS general schedule opens in a new tab or window

Durvalumab is PBS authority opens in a new tab or window 

Cost:
~ $11,270 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, growth factor support 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
Durvalumab 1,500 mg (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes
cARBOplatin 5 AUC (IV infusion) in 500 mL glucose 5% over 30 to 60 minutes (if estimated GFR is greater than 125 mL/min (i.e. 5 AUC dose greater than 750 mg), obtaining direct measurement rather than an estimated kidney function is strongly recommended)
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) ONCE a day (or in divided doses) with or after food. Note: dexamethasone doses on day 2 and 3 may not be required and may be reduced or omitted at the clinician's discretion **
Etoposide 100 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes *

Frequency:
21 days
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Cycle 5 and further cycles

Day 1
Durvalumab 1,500 mg (IV infusion) in 250 mL sodium chloride 0.9% over 60 minutes

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

**Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
28 days 
Cycles:
4 of chemotherapy combination, followed by continuous treatment with durvalumab until disease progression or unacceptable toxicity

Indications

  • First line treatment of small cell lung cancer, extensive disease
  • ECOG performance status 0 or 1.

Precautions:

If any of these conditions are present, clinical judgement should be used and individual cases discussed with an expert in the field as indicated:

  • significant autoimmune disease (e.g. myasthenia gravis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, autoimmune ocular disease)
  • organ transplantation
  • previous history of viral hepatitis
  • HIV/acquired immune deficiency syndrome (AIDS)
  • previous radiation to the lungs.
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.

High risk with carboplatin. Hypersensitivity risk increases with number of cycles of carboplatin. Rechallenge with carboplatin after hypersensitivity carries a high risk of anaphylaxis, and where clinically indicated, should be undertaken with a desensitisation protocol with appropriate supports in place. Refer to local institutional policy.

Read more about Hypersensitivity reaction
Emetogenicity MODERATE

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. 

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.
Carboplatin dosing

Directly measured glomerular filtration rate (mGFR) is the preferred kidney function value in the Calvert formula, especially in patients with either:

  • curative treatment intent
  • clinical situations where estimated kidney function may be unreliable for accurate therapeutic dosing such as
    • eGFR > 125mL/min/1.73 m2
    • eGFR ≤ 45 mL/min/1.73 m2
  • extremes of body size or muscle mass
  • amputees
  • paraplegics.

In all other clinical situations, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative to directly mGFR for use in the Calvert formula.
Immune-related adverse events (irAEs)

Immune-related adverse events (irAEs) can occur early and escalate quickly in patients receiving immune checkpoint inhibitors. irAEs can also occur after discontinuation of treatment. Fatalities have been reported. Management of irAEs is largely based on expert opinion and consensus guidelines.

Examples of irAEs with high risk of mortality include:

  • cardiac toxicity: myocarditis
  • musculoskeletal toxicity: myositis
  • neurological toxicity: encephalitis, Guillain-Barré syndrome, myelitis, myasthenia gravis
  • pulmonary toxicity: pneumonitis
  • skin toxicity: Stevens-Johnson syndrome, toxic epidermal necrolysis.

Examples of irAEs in order of frequency include:

  • Common
    • endocrinopathies: thyroid dysfunction
    • gastrointestinal toxicity: diarrhoea
    • musculoskeletal toxicity: arthralgia, myalgia
    • skin toxicity: rash, erythema, pruritus
  • Less common
    • endocrinopathies: hypophysitis, type I diabetes mellitus
    • gastrointestinal toxicity: colitis
    • musculoskeletal toxicity: inflammatory arthritis
    • ocular toxicity: dry eye
    • renal toxicity
    • skin toxicity: vitiligo
  • Rare
    • endocrinopathies: primary adrenal insufficiency
    • gastrointestinal toxicity: pancreatitis
    • haematological toxicity
    • musculoskeletal toxicity: vasculitis
    • ocular toxicity: uveitis, iritis.

Proactive monitoring, patient self-monitoring and early reporting of adverse events is critical. Treatment interruptions/discontinuation, consultation with specialist and administration of corticosteroids and/or supportive care is required to minimise the risk of death.

Read more about the management of immune-related adverse events (irAEs)
Baseline investigations

Consider ECG and troponin at baseline. There is no clear evidence regarding the efficacy/value of baseline ECG or troponin in patients receiving immune checkpoint inhibitor therapy. Some cancer specialists obtain baseline testing, and others continue this through the initial period of therapy. Consider urinalysis at baseline, particularly in patients with additional risk factors for developing immune-related acute kidney injury.
Blood tests

FBC, EUC, eGFR, LFTs, calcium, magnesium, serum cortisol, TFTs and BSL at baseline.

Repeat FBC, EUC, eGFR, LFTs and BSL prior to each cycle. Check TFTs every 4-6 weeks during treatment and every 12 weeks as indicated after finalising treatment. Consider checking serum cortisol every 4-6 weeks during treatment and every 12 weeks as indicated after finalising treatment. Calcium and magnesium as clinically indicated. Check lipase and amylase if symptomatic of pancreatitis. 

Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g., eGFR) alters by greater than 20% or when there is a change in the clinical status of the patient.

In the absence of suspicion of immune related adverse events less frequent monitoring may be applicable, according to institutional guidelines. Evidence for the frequency of routine blood testing with immunotherapies varies within published studies and guidelines.

Read more about immunotherapy blood test monitoring recommendations
Hepatitis and HIV

Hepatitis screening is recommended in all patients who are to receive immune checkpoint inhibitors.

Immunotherapy is associated with inflammatory adverse reactions resulting from increased or excessive immune activity and patients are at risk of developing autoimmune hepatitis. It should be used with caution in patients who have a history of chronic hepatic infections (hepatitis B and C), detectable human immunodeficiency virus (HIV) viral load or acquired immune deficiency syndrome (AIDS).
Vaccinations

Live vaccines are contraindicated in cancer patients receiving immunosuppressive therapy and/or who have poorly controlled malignant disease.
Live vaccines are not recommended for patients receiving immunotherapy. Caution is advised with inactivated vaccines, particularly the influenza vaccine.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Effects of cancer treatment on fertility

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment.

Studies to evaluate the effects of immune checkpoint inhibitor therapy on fertility have not been performed. Therefore, the effect on male and female fertility is unknown. Limited evidence supports that immune checkpoint inhibitor-related hypogonadism due to orchitis and hypophysitis can impact fertility. Immune checkpoint inhibitors can cause fetal harm when given to pregnant women. A pregnancy test should be considered 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. There is very limited evidence to provide guidance regarding contraception timelines. Some studies have demonstrated PD-1 receptor occupancy for greater than 9 months after anti-PD-1 therapy (Brahmer et al., 2010). As a result, some cancer specialists advise using contraception for at least six months or even as long as two years after treatment finishes.

Read more about the impact of cancer treatment on fertility opens in a new tab or window

Link to Brahmer et al., 2010 opens in a new tab or window
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) opens in a new tab or window unless otherwise specified. Renal and hepatic dose modifications have been standardised where possible. For more information see dosing considerations & disclaimer.

Immune checkpoint inhibitor dose modifications

  • Dose reduction is not recommended
  • No dose adjustment is required in the elderly or mild hepatic impairment. Immune checkpoint inhibitors have not been studied in patients with moderate to severe hepatic impairment.

Management of immune-related adverse events (irAEs)

Link to Management of immune-related adverse events (irAEs)

Chemotherapy dose modifications

Note: All dose reductions are calculated as a percentage of the starting dose

Haematological toxicity
ANC x 109/L (pre-treatment blood test)
1.0 to less than 1.5 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well
0.5 to less than 1.0 Delay treatment until recovery
less than 0.5 Delay treatment until recovery and reduce carboplatin and etoposide by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and reduce carboplatin and etoposide by 25% for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 The general recommendation is to delay, however if the patient is clinically well it may be appropriate to continue treatment; refer to treating team and/or local institutional guidelines
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and reduce carboplatin and etoposide by 25% for subsequent cycles
Kidney dosing recommendations 
  • Suggested dose modifications are based on the International Consensus Guideline on Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD).
  • Where one or more drugs in a protocol is recommended to be avoided, consider using a clinically appropriate alternative treatment protocol instead.
  • Before dose adjusting or omitting a drug, consider treatment intent.
  • In kidney replacement therapy consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 
  • For complete information on individual drug recommendations please review the individual drug monograph in the ADDIKD guideline.
eGFR
(mL/min/1.73m2)		 Carboplatin Durvalumab Etoposide
≥ 60

Target AUC using Calvert formula

Full dose

Full dose
45 - 59

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose

Full dose

Increased risk of haematological adverse events
30 - 44

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose

Consider 25% reduction

Increased risk of haematological adverse events
15 - 29

Target AUC using Calvert formula

Increased risk of adverse events*

Full dose 

Reduce by 25%

Increased risk of haematological adverse events
< 15
(without kidney replacement therapy)

Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 

Full dose

 Consult a multidisciplinary team consisting of oncology/haematology with nephrology and/or clinical pharmacology for the management of dosing. 

* Increased risk of haematological adverse events especially in patients with either a poor performance status, extensive prior anticancer treatment, or concomitant nephrotoxic drug exposure,

Consider if immune-related adverse event. See Management of immune-related adverse events (irAEs)
Hepatic impairment
Hepatic dysfunction
Consider if immune-related adverse event. See Management of immune-related adverse events (irAEs)
Mild Reduce etoposide by 25%
Moderate Reduce etoposide by 50%
Severe Omit etoposide
Mucositis and stomatitis
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce doses for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce carboplatin and etoposide by 25%
3rd occurrence: Reduce carboplatin and etoposide by 50%
4th occurrence: Omit carboplatin and etoposide
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce doses for subsequent cycles as follows:
1st occurrence: Reduce carboplatin and etoposide by 50%
2nd occurrence: Omit carboplatin and etoposide

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.

Carboplatin
  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
Paclitaxel Administration schedule may influence the development of myelosuppression Minimise toxicity by administering paclitaxel first in regimens using the combination
Durvalumab
No formal pharmacokinetic drug interaction studies have been conducted with durvalumab. Since durvalumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.
  Interaction Clinical management
Immunosuppressants (inc. corticosteroids) Reduced efficacy of both immunosuppressants and durvalumab possible due to pharmacodynamic interaction

It is recommended that patients requiring corticosteroids prior to treatment receive the lowest possible dose (preferably no greater than 10 mg prednisolone or equivalent steroid per day). Once started on durvalumab the use of corticosteroids to treat immune related adverse events (irAEs) does not appear to impact the clinical response to durvalumab. In patients requiring ongoing corticosteroids post management of an irAE, the dose should be as low as possible.

Monitor for signs of organ rejection in transplant recipients.
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 opens in a new tab or window and P‑gp opens in a new tab or window inhibitors. If treating VTE, avoid use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window inducers. 

Rivaroxaban: avoid concurrent use with strong CYP3A4 opens in a new tab or window and P‑gp opens in a new tab or window  inhibitors.

Dabigatran: avoid combination with strong P‑gp opens in a new tab or window 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 opens in a new tab or window

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 or address chemical compatibilities related to IV drug preparation and administration. 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 opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1

Approximate treatment time: 3.5 hours

Pre treatment assessment

Check for adverse events during previous treatment.

Any toxicity may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Immunotherapy patient assessment tool prior to each treatment.

Prior to administration

Prime required IV lines with sodium chloride 0.9%: 

  • a low protein binding 0.2 or 0.22 micron inline filter must be used for durvalumab
  • ensure a separate line and filter is used for durvalumab
  • attach a second IV line via a luer lock connector as close as possible to the site of injection, this may be required in case of an infusion-related reaction (IRR) or a hypersensitivity reaction.

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify premedication and antiemetics taken or administer as prescribed, if required.

Verify dexamethasone taken or administer as prescribed.

Durvalumab

Administer durvalumab:
  • via IV infusion over 60 minutes 
  • observe for infusion-related reactions
  • flush with 50 mL of sodium chloride 0.9%.
Infusion-related reaction (IRR)

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

Grade 1 or 2:
  • consider holding or decreasing the rate of infusion, alert medical officer and monitor closely 
  • administer symptomatic medications as prescribed
  • further doses require close monitoring, premedications should be considered and prescribed by the medical officer as per local policy.
Grade 3 or 4: 
  • stop infusion immediately 
  • medical officer review. 

Carboplatin 

Administer carboplatin (irritant):
  • via IV infusion over 30 to 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 may occur within minutes of administration.
Infusion-related reaction (IRR)

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

Grade 1 or 2:

  • slow or hold rate of infusion, alert medical officer and monitor closely
    • if symptoms are mild and resolve when infusion is stopped, consider recommencing infusion after review by medical officer at a slower rate
    • administer symptomatic medications as prescribed
  • further doses require close monitoring, premedications should be considered and prescribed by the medical officer as per local policy.
Grade 3 or 4: 
  • stop infusion immediately 
  • seek urgent medical officer review, do not restart the infusion.

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 (IRR)

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.

Post administration

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Days 2 and 3

Approximate treatment time: 90 minutes

Pre treatment assessment

Any toxicity grade 2 or greater may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Anti-cancer drug patient assessment tool prior to each day of treatment.

Prior to administration

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify antiemetics taken or administer as prescribed.

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 (IRR)

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.

Post administration

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Discharge information

Discharge medications

Antiemetics - as/if prescribed.

Patient information

Ensure patient receives protocol patient information sheet.

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 or address chemical compatibilities related to IV drug preparation and administration. 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 opens in a new tab or window and Australian Injectable Drugs Handbook opens in a new tab or window websites for further information.

eviQ is currently updating the way information is presented in the administration section, if you notice any discrepancies please let us know, via feedback@eviq.org.au.

Day 1

Approximate treatment time: 90 minutes

Pre treatment assessment

Check for adverse events during previous treatment.

Any toxicity may require dose reduction, delay or omission of treatment and review by medical officer before commencing treatment.

Immunotherapy patient assessment tool prior to each treatment.

Prior to administration

Prime required IV lines with sodium chloride 0.9%: 

  • a low protein binding 0.2 or 0.22 micron inline filter must be used for durvalumab
  • ensure a separate line and filter is used for durvalumab
  • attach a second IV line via a luer lock connector as close as possible to the site of injection, this may be required in case of an infusion-related reaction (IRR) or a hypersensitivity reaction.

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify premedication and antiemetics taken or administer as prescribed, if required.

Durvalumab

Administer durvalumab:
  • via IV infusion over 60 minutes 
  • observe for infusion-related reactions
  • flush with 50 mL of sodium chloride 0.9%.
Infusion-related reaction (IRR)

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

Grade 1 or 2:
  • consider holding or decreasing the rate of infusion, alert medical officer and monitor closely 
  • administer symptomatic medications as prescribed
  • further doses require close monitoring, premedications should be considered and prescribed by the medical officer as per local policy.
Grade 3 or 4: 
  • stop infusion immediately 
  • medical officer review. 

Post administration

Remove IV cannula and/or deaccess TIVAD or CVAD. 

Continue safe handling precautions (reproductive risk only) for 7 days after completion of drug(s).

Discharge information

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.

There can be an overlap between the immune-related and chemotherapy-related adverse events with this treatment. Immune-related adverse events (irAEs) can escalate quickly and close monitoring of the patient is required. Immune-related symptoms should improve promptly after the introduction of immunosuppressive therapy. If this does not occur review the diagnosis and seek further specialist advice. Refer to the Management of immune related adverse events document for further information.

Immune related adverse events
Cardiotoxicity

Cardiotoxicity is a rare but serious side effect, which may manifest as asymptomatic reduction in left ventricular ejection fraction (LVEF), arrhythmia, cardiomyopathy, myocarditis, pericarditis, cardiac fibrosis, hypertension, cardiac ischaemia, congestive heart failure (CHF) and cardiac arrest.

Read more about Management of immune related adverse events.
Gastrointestinal toxicity

Colitis, diarrhoea or more bowel movements than usual; blood or mucous in stools; dark, tarry, sticky stools; abdominal pain or tenderness.

Upper gastrointestinal tract inflammation including gastritis, duodenitis and oesophagitis can occur less commonly. Symptoms include nausea, vomiting, dysphagia, odynophagia, haematemesis and abdominal pain.

Read more about Management of immune related adverse events
Haematological toxicity

Autoimmune haemolytic anaemia (AIHA), acquired thrombotic thrombocytopenic purpura (TTP), aplastic anaemia (AA), immune thrombocytopenia (ITP), acquired haemophilia (AH), haemolytic uremic syndrome (HUS) and lymphopenia are rare but potentially serious immune-related adverse events associated with immunotherapy treatment.

Read more about Management of immune related adverse events.
Hepatotoxicity

Transaminase and total bilirubin elevation, jaundice, severe nausea or vomiting, pain on the right side of the abdomen, drowsiness, dark urine, bleeding or bruising more easily than normal, anorexia.

Read more about Management of immune related adverse events.
Musculoskeletal toxicity

Inflammatory arthritis, temporal arteritis, arthralgia, myalgia, synovitis, vasculitis, polymyalgia-like syndrome and myositis.

Read more about Management of immune related adverse events.
Neurological toxicity

Aseptic meningitis, myasthenia gravis, Guillain-Barre syndrome, encephalitis, meningeal symptoms, optic neuritis, neuropathy and acute inflammatory demyelinating polyneuropathy are infrequent but potentially serious immune-related adverse events associated with immunotherapy treatment.

Read more about Management of immune related adverse events.
Ocular toxicity

Eye pain, blurred vision, Uveitis/iritis, episcleritis, blepharitis, optic neuritis, tear duct stenosis, conjunctivitis, hyperlacrimation, watery or dry eyes and photophobia. 

Read more about Management of immune related adverse events.
Other endocrinopathies

Type 1 diabetes mellitus, hypophysitis, hypopituitarism and adrenal insufficiency are infrequent but potentially serious immune-related adverse events associated with immunotherapy treatment.

Read more about Management of immune related adverse events
Pulmonary toxicity

Radiographic changes, dyspnoea, new or worsening cough, hypoxia, tachycardia, chest pain or fever.

Read more about Management of immune related adverse events.
Renal toxicity

Increase in serum creatinine, oliguria, haematuria, peripheral oedema and anorexia.

Read more about Management of immune related adverse events.
Skin toxicity

Rash including full thickness, pruritus, skin blisters, ulceration and necrosis. Radiation recall can occur at site of previous radiation therapy. Symptoms include vesiculation, desquamation and ulceration of the skin.

Read more about Management of immune related adverse events
Thyroid toxicity

Thyroid toxicity is common with immune checkpoint inhibitors. Hypothyroidism is most frequent however hyperthyroidism can also occur.

Read more about Management of immune related adverse events

Chemotherapy 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

Chemotherapy early (onset days to weeks)
Headache
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 and stomatitis

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
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Diarrhoea

Read more about treatment induced diarrhoea
Fatigue

Read more about fatigue

Chemotherapy 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

The evidence supporting this protocol is provided by a phase III, multicentre, international, randomised trial (CASPIAN) involving 805 patients.r

Between March 2017, and May 2018, 805 patients with extensive stage SCLC were randomised 1:1:1, with 268 receiving durvalumab plus platinum–etoposide, 268 receiving durvalumab plus tremelimumab plus platinum-etoposide and 269 receiving platinum–etoposide alone. Platinum-etoposide consisted of etoposide 80–100 mg/m2 intravenously on days 1 to 3 with investigator's choice of either carboplatin AUC 5–6 or cisplatin 75–80 mg/m2 intravenously on day 1 of each 3-week cycle. Patients in the immunotherapy groups received up to four cycles of platinum-etoposide plus durvalumab 1,500 mg with or without termelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1,500 mg every 4 weeks. Maintenance therapy was continued until disease progression or unacceptable toxicity. Patients in the platinum-etoposide group could receive an additional two cycles of platinum-etoposide (up to 6 cycles in total) and prophylactic cranial irradiation (PCI) after chemotherapy at the investigator’s discretion. Crossover was not allowed.r

The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), objective response (OR), OS at 18 months, PFS at 6 and 12 months and safety.

Efficacy

At the planned exploratory analysis at 3 years, after a median follow up of 39.4 months (range 0.1-47.5 months), the significant improvement in OS demonstrated in the durvalumab plus platinum–etoposide group was maintained (HR 0.71 [95% CI 0.60-0.86; P=0.0003]).r The median OS was 12.9 months (95% CI 11.3-14.7) in patients receiving durvalumab plus platinum–etoposide, compared with only 10.5 months (95% CI 9.3–11.2) in those who received platinum–etoposide alone. 36 month OS rates were, 17.6% (95% CI 13.3-22.4) of patients in the durvalumab plus platinum–etoposide (EP) group were alive, compared with only 5.8% (95% CI 3.4-9.1) in those who received platinum–etoposide alone.r

PFS or response data were not collected beyond the previous data cut-off in January 2020 as PFS was sufficiently mature (87% data maturity). At that time, median PFS was not significantly different between the two groups, measuring 5.1 months (95% CI 4.7–6.2) with durvalumab plus platinum–etoposide and 5.4 months (4.8–6.2) with platinum-etoposide alone. 6-month PFS survival rates were 45% (39.3-51.3) vs 46% (39.3-51.7); however, the 12-month PFS rates were notably higher in the durvalumab plus platinum–etoposide group, at 18% (95% CI 13.1–22.5) compared with 5% (95% CI 2.4–8.0) in the platinum–etoposide group.r​

At the January 2020 data cut-off, median follow-up was 25.1 months. Post hoc analysis demonstrated a confirmed objective response in 182 (68%) of the 268 patients who received durvalumab plus platinum–etoposide, compared with 155 (58%) of the 269 patients who received platinum–etoposide alone, (OR 1.56 [1.10–2.22]).r​

Kaplan-Meier of OS in the ITT population: durvalumab plus EP versus EPr

© ESMO open 2022

Kaplan-Meier of PFS for durvalumab plus EP versus EPr 

© Lancet Oncol 2021

Toxicity

Any-cause grade 3 or 4 adverse events occurred in 163 (62%) of the 265 patients treated with durvalumab plus platinum–etoposide and 166 (62%) of the 266 patients treated with platinum–etoposide alone.​r

In the updated analysis, serious adverse events were reported in 86 (32%) patients in the durvalumab plus platinum-etoposide group and 97 (36%) in the platinum-etoposide group.r Adverse events leading to treatment discontinuation of at least one study drug occurred in 27 (10%) of patients in the durvalumab plus platinum-etoposide group and 25 (9%) in the platinum-etoposide group.r 

Immune-related adverse events (irAEs) were reported in 52 (20%) of the 265 patients treated with durvalumab plus platinum–etoposide and seven (3%) of the 266 patients treated with platinum–etoposide alone. Most of these events were grade 1 or 2, and grade 3 or 4 irAEs were only identified in 12 (5%) patients in the durvalumab plus platinum–etoposide group and one patient (<1%) in the platinum–etoposide group. The most common irAEs were grade 1 or 2 thyroid-related events with hypothyroid events affecting 24 patients (9%) treated with durvalumab plus platinum etoposide and two patients (1%) treated with platinum etoposide and hyperthyroid events affecting 14 patients (5%) and none respectively.r

Two deaths (1%) occurred in the durvalumab plus platinum-etoposide group (hepatotoxicity and interstitial lung disease). There was one death (<1%) in the platinum-etoposide group due to pneumonitis.r

Adverse events of any cause (safety population)r

© Lancet Oncol 2021

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Version 4

Date Summary of changes
20/11/2024 Protocol reviewed at the Respiratory Reference Committee Meeting on 18/10/2024. Evidence updated with 3 year analysis of CASPIAN. Following the meeting carboplatin dose capping note removed from detailed treatment schedule. Version number increased to V.4. Review in 2 years.

Version 3

Date Summary of changes
08/02/2024

Protocol updated with ADDIKD guideline recommendations. New kidney dosing recommendation table added to dose modification section.

PDF of previous protocol.

Version number changed to V.3.
03/04/2024 Patient information side effects preamble updated to include examples of 'common, less common and rare' side effects following consensus at the immunotherapy and skin reference committee meeting held on 23rd of February 2024. 

Version 2

Date Summary of changes
13/04/2022

Protocol updated based on the consensus gained at immunotherapy reference committee meeting held on 4th of March 2022. The following changes have been made across all immune checkpoint inhibitor protocols:

  • Clinical information- general irAEs, hepatitis and HIV, and fertility blocks updated. Individual irAE-related blocks removed. New block (baseline investigations) added.
  • Side effects- preamble wording updated.
  • Patient information- side effect section preamble wording updated. Pregnancy and breastfeeding block in general advice section updated.

Version number increased to V.2.
20/05/2022 Protocol reviewed electronically by Medical Oncology Reference Committee. No change. Next review in 2 years.
01/12/2023 Durvalumab drug status updated to PBS authority.

Version 1

Date Summary of changes
22/02/2021 Protocol approved electronically by Medical Oncology Reference Committee.
01/03/2021 Protocol approved and published on eviQ. Review 1 year.

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

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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/3921

06 Jun 2025