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Colorectal adjuvant capecitabine

 Fluoropyrimidine overdose or overexposure:

Fluoropyrimidine overdose or overexposure may result in severe or life-threatening toxicity. An antidote is available and is highly effective if given within 96 hours.  Read more about fluoropyrimidine overdose or overexposure.

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

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Cycle 1 to 8

Drug Dose Route Day
Capecitabine 1,250 mg/m2 TWICE a day PO 1 to 14
Frequency:
21 days 
Cycles:
8 
Notes:

Recent evidence from a meta-analysis examining duration of oxaliplatin based therapy in stage III colon cancer has demonstrated:r 

  • In the overall population shorter therapy (3 months) was not equivalent to longer (6 months) therapy
  • For low risk patients (T1-3N1) shorter CapOx was equivalent to longer with less neurotoxicity
  • ​For patients being treated with FOLFOX 6 months was superior to 3 months
  • For high risk patients 6 months of therapy is recommended as 3 months appears inferior

Non-oxaliplatin based adjuvant therapy was not examined in this study and should be given for 6 months

Drug status:

Capecitabine is on the PBS general schedule

Capecitabine is available as 150 mg and 500 mg tablets

Cost:
~ $130 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), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

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.

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 8

Day 1 to 14
Capecitabine 1,250 mg/m2 (PO) TWICE a day within 30 minutes after the end of a meal
Frequency:
21 days 
Cycles:
8 

Cycle 1 to 8

Drug Dose Route Day
Capecitabine 1,250 mg/m2 TWICE a day PO 1 to 14
Frequency:
21 days 
Cycles:
8 
Notes:

Recent evidence from a meta-analysis examining duration of oxaliplatin based therapy in stage III colon cancer has demonstrated:r 

  • In the overall population shorter therapy (3 months) was not equivalent to longer (6 months) therapy
  • For low risk patients (T1-3N1) shorter CapOx was equivalent to longer with less neurotoxicity
  • ​For patients being treated with FOLFOX 6 months was superior to 3 months
  • For high risk patients 6 months of therapy is recommended as 3 months appears inferior

Non-oxaliplatin based adjuvant therapy was not examined in this study and should be given for 6 months

Drug status:

Capecitabine is on the PBS general schedule

Capecitabine is available as 150 mg and 500 mg tablets

Cost:
~ $130 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), MIMS Online and other sources. These costs are reviewed and updated on eviQ at 6 monthly intervals.

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.

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 8

Day 1 to 14
Capecitabine 1,250 mg/m2 (PO) TWICE a day within 30 minutes after the end of a meal
Frequency:
21 days 
Cycles:
8 
  • Adjuvant stage III colorectal cancer after complete resection of the primary tumour.
Safety alert fluoropyrimidines

Fluoropyrimidines can be administered by different routes and schedules with each method having associated increased risk of certain side effects. Fluoropyrimidine overdose or overexposure is a rare but potentially life threatening side effect of this drug class and can occur by any route of administration. An antidote is available and highly effective if given within 96 hours.

Read more about the medication safety alert for infusional fluorouracil and fluoropyrimidine overdose or overexposure
Caution with oral anti-cancer drugs

Select links for information on the safe prescribing, dispensing and administration of orally administered anti-cancer drugs. 

Read more about the COSA guidelines and oral anti-cancer therapy
Emetogenicity LOW

Antiemetics are not routinely required; however should a patient experience 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 may be administered.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Cardiac toxicity

Angina-like chest pain, tachycardia, arrhythmias, heart failure, myocardial infarction and cardiac arrest may occur with capecitabine especially in patients with a prior history of coronary artery disease.

Cardiac symptoms may require cessation of capecitabine and referral to a cardiologist for symptomatic treatment. Re-challenge is controversial and generally not recommended.

Read more about cardiac toxicity associated with anti-cancer drugs
Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency

Rare, life-threatening toxicities such as mucositis, neutropenia, neurotoxicity and diarrhoea have been reported following administration of fluoropyrimidines (e.g. fluorouracil and capecitabine). Severe unexplained toxicities require investigation prior to continuing with treatment. Testing for DPD enzyme deficiency is available in Australia but not currently reimbursed.

Read more about dihydropyrimidine dehydrogenase (DPD) enzyme deficiency
Diarrhoea

Antidiarrhoeals (e.g. loperamide) are usually prescribed with this treatment.

Read more about treatment induced diarrhoea
Hyperbilirubinaemia

Capecitabine can induce hyperbilirubinaemia which may require an interruption in treatment (see dose modifications).
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 and LFTs at baseline and prior to each cycle. INR as clinically indicated.
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, including BCG, MMR, zoster and varicella 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.
Effects of cancer treatment on fertility

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

Read more about the effect 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 and reference committee consensus. 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: all dose reductions are calculated as a percentage of the starting dose.

Haematological toxicity
ANC x 109/L (pre-treatment blood test) 
0.5 to less than 1.0 Delay treatment until recovery
less than 0.5 Delay treatment until recovery and consider reducing capecitabine by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing capecitabine by 25% for subsequent cycles
Platelets x 109/L (pre-treatment blood test)
75 to less than 100 Refer to local institutional guidelines; it is the view of the expert clinicians that treatment should continue if patient is clinically well. 
50 to less than 75 Delay treatment until recovery
less than 50 Delay treatment until recovery and consider reducing capecitabine by 25% for subsequent cycles
Renal impairment
Creatinine clearance (mL/min)
30 to 50 Reduce capecitabine by 25%
less than 30 Omit capecitabine
Hepatic impairment
Hepatic dysfunction
Mild No dose modifications necessary
Moderate Reduce capecitabine by 25%
Severe Reduce capecitabine by 50%
Treatment related Grade 3 or Grade 4 hyperbilirubinaemia  Delay treatment until toxicity resolves to Grade 2 or less and reduce the dose of capecitabine for subsequent cycles as recommended above
Mucositis and stomatitis
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce capecitabine by 25%
3rd occurrence: Reduce capecitabine by 50%
4th occurrence: Omit capecitabine
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce capecitabine by 50%
2nd occurrence: Omit capecitabine
Diarrhoea
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce capecitabine 25%
3rd occurrence: Reduce capecitabine by 50%
4th occurrence: Omit capecitabine
Grade 3 or Grade 4 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce capecitabine by 50%
2nd occurrence: Omit capecitabine
Hand foot syndrome (link to Hand foot syndrome (Palmar-plantar erythrodysaesthesia)
Grade 2 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: No dose reduction
2nd occurrence: Reduce capecitabine by 25%
3rd occurrence: Reduce capecitabine by 50%
4th occurrence: Omit capecitabine
Grade 3 Delay treatment until toxicity has resolved to Grade 1 or less and reduce the dose for subsequent cycles as follows:
1st occurrence: Reduce capecitabine by 50%
2nd occurrence: Omit capecitabine

Drug interactions in eviQ protocols are under review and being updated to align with current literature. Further site-wide updates and changes will occur in due course. References & Disclaimer

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: 

Capecitabine
  Interaction Clinical management

Sorivudine* and analogues (e.g. brivudine*)

 Potentially fatal increased toxicity of fluorouracil, the active metabolite of capecitabine, due to reduced clearance Combination contraindicated and at least 4 weeks must elapse between the end of treatment with sorivudine (or analogues, such as brivudine) and the start of capecitabine therapy
Warfarin and other drugs metabolised by CYP2C9 (e.g. phenytoin etc.) Increased effects/toxicity of these drugs possible due to inhibition of CYP2C9 by capecitabine and/or its metabolites resulting in reduced clearance Avoid combination or monitor for increased effect/toxicity. (e.g. INR can be increased by 91% in patients on warfarin)

* currently not marketed in Australia

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

Days 1 to 14

This is an oral treatment

General patient assessment prior to each treatment.

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

Capecitabine

  • administer orally TWICE a day on days 1 to 14
  • to be swallowed whole with a glass of water; do not break, crush or chew
  • to be taken morning and night (approximately 12 hours apart) within thirty minutes after the end of a meal
  • tablets may also be dispersed in water if patient has swallowing difficulties:
    • place the required number of tablets in a disposable cup and fill with approximately 200mL of water, leave the tablets to dissolve (approximately 15 minutes) and swallow immediately
    • mix any residues in the cup with water and swallow
    • avoid direct contact of the tablets or solution with the skin or mucous membrane. If such contact occurs, wash thoroughly.

Note: missed doses should not be replaced; if a dose is forgotten or vomited, normal dosing should be resumed at the next scheduled dose.

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

Discharge information

Capecitabine tablets
  • Capecitabine tablets with written instructions on how to take them.
Antiemetics
  • Antiemetics as prescribed.
Antidiarrhoeals
  • Antidiarrhoeals as prescribed.
Patient information
  • Ensure patient receives 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)
Nausea and vomiting

Read more about prevention of treatment induced nausea and vomiting
Cardiotoxicity

Coronary artery spasm is a temporary, sudden narrowing of one of the coronary arteries that may present at any time during treatment with fluoropyrimidines. It most commonly manifests as angina.
Taste and smell alteration

Read more about taste and smell changes

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 neutropenia
Thrombocytopenia

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

Read more about thrombocytopenia
Diarrhoea

Read more about treatment induced diarrhoea
Anorexia

Loss of appetite accompanied by decreased food intake.

Read more about anorexia
Oral mucositis

Erythematous and ulcerative lesions of the gastrointestinal tract (GIT). It commonly develops following chemotherapy, 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
Actinic keratoses flare

Pre-existing actinic keratoses (AKs) can become more inflamed and scaly as a result of immunosuppression. 

Read more about actinic keratoses flare
Skin rash

Anti-cancer drugs can cause a number of changes in the skin with maculo-papular rash the most common type of drug-induced skin reaction. 

Read more about skin rash
Palmar-plantar erythrodysaesthesia (PPE) - hand-foot syndrome (HFS)

Bilateral erythema, tenderness, pain, swelling, tingling, numbness, pruritus, dry rash, or moist desquamation and ulceration of the palms and soles. It is also known as hand-foot syndrome (HFS). Symptoms appear to be dose dependent and palms are affected more than soles.

Read more about hand-foot syndrome associated with chemotherapy
Fatigue

Read more about fatigue
Abdominal pain

Dull ache, cramping or sharp pains are common with some anti-cancer drugs. These are caused by either increased or decreased gastrointestinal motility and can be associated with diarrhoea or constipation.
Ocular changes

Symptoms may include eye pain, blurred vision, blepharitis, uveitis, optic neuritis, tear duct stenosis, conjunctivitis, hyperlacrimation, watery or dry eyes and photophobia. 
Photosensitivity

Increased sensitivity to ultraviolet (UV) light resulting in an exaggerated sunburn-like reaction accompanied by stinging sensations and urticaria.

Late (onset weeks to months)
Anaemia

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

Read more about anaemia
Hyperbilirubinaemia

An abnormal increase in the amount of bilirubin circulating in the blood which may result in jaundice.

The evidence supporting this protocol is provided by a multicentre randomised open-label phase III trial (X-ACT) involving 1987 patients comparing capecitabine with bolus 5-FU/FA (Mayo clinic regimen) in the postoperative adjuvant setting in patients with Stage III colon cancer. Patients with Stage II colon cancer or rectal cancer were excluded from this study and the upper age limit for entry was 75 years.r

Between November 1998 and November 2001, 1004 patients were randomised to receive capecitabine 1250 mg/m2 twice daily on days 1-14 of a 21-day cycle for 8 cycles and 983 patients were randomised to receive a rapid infusion of FA 20 mg/m2 and IV bolus 5-FU 425 mg/m2 on days 1-5 of a 28-day cycle for 6 cycles.

The primary end point of the study was disease-free survival (DFS) and secondary end points were overall survival (OS) and relapse-free survival (RFS). The study was powered to establish non-inferiority.r

Efficacy

After a median follow-up of 6.9 years, capecitabine was at least equivalent to bolus 5-FU/FA in terms of disease-free survival (DFS) [hazard ratio (HR)= 0.88; 95% CI 0.77 to 1.01] and overall survival (OS) [HR=0.86; 95% CI 0.74 to 1.01). This pattern was maintained in all subgroups, including patients aged > 70 years.r

Disease-free survival in patients who received (A) capecitabine (B) 5-fluorouracil/folinic acidr

© Annals of Oncology 2012

Toxicity

Most patients received the designated number of treatment cycles (83% in the capecitabine arm and 87% in the 5-FU/FA arm). Dose modifications were required in 57% of patients receiving capecitabine versus 52% receiving 5-FU/FA. More interruptions (15% vs 5%) and delays (46% vs 29%) were also required with capecitabine.r

There was a statistically higher incidence of hand and foot syndrome (60% vs 9%) and hyperbilirubinaemia (50% vs 20%) in patients treated with capecitabine and higher diarrhoea (64% vs 46%), nausea or vomiting (51% vs 36%), stomatitis (60% vs 22%), alopecia (22% vs 6%) and neutropenia (63% vs 32%) with 5-FU/FA. It should be noted that the toxicity profile of 5-FU/FA is reflective of the Mayo regimen which is the most toxic of the 5-FU/FA administration schedules.

In both treatment groups, scores for global health status (EORTC-QLQ-C30) were constant over time (from baseline to 25 weeks of the trial treatment) and there were no statistically significant differences between groups.r​

Adverse eventsr​

© New England Journal of Medicine 2005

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Version 5

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

Version 4

Date Summary of changes
11/04/2007 Independent evaluation added.
01/08/2007 Patient information updated.
15/08/2009 Review, new dose modifications and transferred to eviQ.
01/07/2010 Haematological dose modifications updated ( 20% changed to 25% dose reduction; cut-off for platelets for dose reduction changed from 10 x 109/L to 50 x 109/L).
27/10/2010 Cardiotoxicty side effect added to protocol.
27/01/2011 New format to allow for export of protocol information.
Protocol version number changed to V.2.
Antiemetics and premedications added to the treatment schedule.
Additional Clinical Information, Key Prescribing table and Key Administration table combined into new section titled Clinical Considerations.
Drug specific information placed behind the drug name link.
15/3/2012 PHC view updated.
26/07/2012 The concern that fixed dose capecitabine may result in underdosing was raised at the reference committee meeting on 25/11/11.
Group consensus to change capecitabine dose to 1250 mg/m2 BD (was 2000 mg BD) as per original trial.
13/09/2013

Protocol reviewed by reference committee via email.
No changes and next review in 2 years.
25/10/2013 Evidence updated with final results from the X-ACT trial.
24/08/2014 PHC view removed.
18/02/2016 Discussion with Medical Oncology Reference Committee Chairs and protocol to be reviewed every 5 years. Next review due in 3 years.
09/11/2016

The following change made post Medical Oncology Reference Committee meeting held on 21 October 2016: link to AGTIG and ANZCTR added.
16/12/2016 Dissolving capecitabine information added to administration and patient information.
06/03/2017 Acitinic keratoses flare added as a side effect.
31/05/2017 Transferred to new eviQ website. Version number change to V.3.
16/02/2018 Protocol reviewed electronically by Medical Oncology Reference Committee. Fluoropyrimidine warning added. Review in 5 years.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.4.

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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Review due:

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/74

27 Sep 2021