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Breast neoadjuvant/adjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide)

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Cycle 1 to 6

Drug Dose Route Day
DOXOrubicin 50 mg/m2 IV 1
DOCEtaxel 75 mg/m2 IV infusion 1
CYCLOPHOSPHamide 500 mg/m2 IV infusion 1
Pegfilgrastim 6 mg Subcut 2
Frequency:
21 days 
Cycles:
6 (up to 8 cycles for neoadjuvant treatment)
Notes:

Clinical trials have used prophylactic ciprofloxacin 500 mg twice daily on days 5 to 14. An update on pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC is available.1

Drug status:

Doxorubicin, docetaxel and cyclophosphamide are on the PBS general schedule opens in a new tab or window

Pegfilgrastim is PBS authority opens in a new tab or window

Cost:
~ $210 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 6

Day before chemotherapy
Dexamethasone 8 mg (PO) TWICE a day with or after food
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
DOXOrubicin 50 mg/m2 (IV) over 5 to 15 minutes
DOCEtaxel 75 mg/m2 (IV infusion) in 250 mL to 500 mL sodium chloride 0.9% over 60 minutes
CYCLOPHOSPHamide 500 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2
Pegfilgrastim 6 mg (Subcut) inject subcutaneously at least 24 hours post chemotherapy
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food*

*Dexamethasone 4 to 8 mg on day 3 and 4 may be required for those with risk factors for delayed nausea and vomiting. Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
21 days 
Cycles:
6 (up to 8 cycles for neoadjuvant treatment)

Cycle 1 to 6

Drug Dose Route Day
DOXOrubicin 50 mg/m2 IV 1
DOCEtaxel 75 mg/m2 IV infusion 1
CYCLOPHOSPHamide 500 mg/m2 IV infusion 1
Pegfilgrastim 6 mg Subcut 2
Frequency:
21 days 
Cycles:
6 (up to 8 cycles for neoadjuvant treatment)
Notes:

Clinical trials have used prophylactic ciprofloxacin 500 mg twice daily on days 5 to 14. An update on pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC is available.1

Drug status:

Doxorubicin, docetaxel and cyclophosphamide are on the PBS general schedule opens in a new tab or window

Pegfilgrastim is PBS authority opens in a new tab or window

Cost:
~ $210 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 6

Day before chemotherapy
Dexamethasone 8 mg (PO) TWICE a day with or after food
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
DOXOrubicin 50 mg/m2 (IV) over 5 to 15 minutes
DOCEtaxel 75 mg/m2 (IV infusion) in 250 mL to 500 mL sodium chloride 0.9% over 60 minutes
CYCLOPHOSPHamide 500 mg/m2 (IV infusion) in 500 mL sodium chloride 0.9% over 30 to 60 minutes
Day 2
Pegfilgrastim 6 mg (Subcut) inject subcutaneously at least 24 hours post chemotherapy
Dexamethasone 8 mg (PO) ONCE a day (or in divided doses) with or after food*

*Dexamethasone 4 to 8 mg on day 3 and 4 may be required for those with risk factors for delayed nausea and vomiting. Link to ID 7 Prevention of anti-cancer therapy induced nausea and vomiting

Frequency:
21 days 
Cycles:
6 (up to 8 cycles for neoadjuvant treatment)
  • Node-positive or high risk node-negative, HER-2 negative breast cancer.
  • Neoadjuvant treatment for HER-2 negative breast cancer.
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 docetaxel

Read more about Hypersensitivity reaction
Premedication

The product information states that premedication is required for this treatment.
Please refer to the treatment schedule for the suggested premedication regimen.
This may be substituted to reflect institutional policy.

Read more about premedication for prophylaxis of taxane hypersensitivity reactions
Emetogenicity HIGH

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

A combination of an NK1 receptor antagonist, 5HT3, and a steroid is available on the PBS for the prevention of nausea and vomiting associated with all moderate to highly emetogenic anti-cancer therapies. 

A steroid has been included both as an antiemetic and premedication for hypersensitivity in this protocol.

Ensure that patients also have sufficient antiemetics for breakthrough emesis:

Metoclopramide 10 mg three times a day when necessary (maximum of 30 mg/24 hours, up to 5 days) OR

Prochlorperazine 10 mg PO every 6 hours when necessary.

Read more about preventing anti-cancer therapy induced nausea and vomiting
Cumulative lifetime dose of anthracyclines

Cumulative doses should take into account all previous anthracyclines received during a patient’s lifetime (i.e. daunorubicin, doxorubicin, epirubicin, idarubicin and mitoxantrone). 

Criteria for reducing the total anthracycline cumulative lifetime dose include:

  • patient is elderly
  • prior mediastinal radiation
  • hypertensive cardiomegaly
  • concurrent therapy with high dose cyclophosphamide and some other cytotoxic drugs (e.g. bleomycin, dacarbazine, dactinomycin, etoposide, melphalan, mitomycin and vincristine).

Baseline clinical assessments include echocardiogram (ECHO) or gated heart pool scan (GHPS) and electrocardiogram (ECG) evaluation.

Patients with normal baseline cardiac function (left ventricular ejection fraction (LVEF) > 50%) and low risk patients require LVEF monitoring when greater than 70% of the anthracycline threshold is reached or if the patient displays symptoms of cardiac impairment. Post-treatment cardiac monitoring is recommended for patients who have received high levels of total cumulative doses of anthracyclines at the clinician's discretion.

Read more about cardiac toxicity associated with anthracyclines
Peripheral neuropathy

Assess prior to each treatment. If a patient experiences grade 2 or greater peripheral neuropathy, a dose reduction, delay, or omission of treatment may be required; review by medical officer before commencing treatment.

Read more about peripheral neuropathy

Link to Anti-cancer drug induced peripheral neuropathy screening tool
Biosimilar drug

Read more about biosimilar drugs on the Biosimilar Awareness Initiative opens in a new tab or window 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 opens in a new tab or window
Blood tests

FBC, EUC, eGFR and LFTs at baseline and prior to each cycle.
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. Possible suboptimal response to inactivated vaccines.

For more information about vaccinations in people with cancer refer to the Australian Immunisation Handbook opens in a new tab or window.
Fertility, pregnancy and lactation

Cancer treatment can have harmful effects on fertility and this should be discussed with all patients of reproductive potential prior to commencing treatment. There is a risk of fetal harm in pregnant women. A pregnancy test should be considered prior to initiating treatment in females of reproductive potential if sexually active. It is important that all patients of reproductive potential use effective contraception whilst on therapy and after treatment finishes. Effective contraception methods and adequate contraception timeframe should be discussed with all patients of reproductive potential. Possibility of infant risk should be discussed with breastfeeding patients.

Read more about the impact of cancer treatment on fertility 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.

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 docetaxel, doxorubicin and cyclophosphamide by 25% for subsequent cycles
Febrile neutropenia Delay treatment until recovery and consider reducing docetaxel, doxorubicin and cyclophosphamide 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 docetaxel, doxorubicin and cyclophosphamide 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)		 Cyclophosphamide Docetaxel Doxorubicin
≥ 60

Full dose

Full dose

Full dose
45 - 59

Full dose

Full dose 

Full dose
30 - 44

Full dose

Full dose 

Full dose 
15 - 29

Full dose

Potential for increased risk of adverse events

Full dose

Full dose 
< 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

Full dose
Hepatic impairment
Hepatic dysfunction
Minimal Reduce docetaxel by 25%
Mild Reduce doxorubicin by 25% and docetaxel by 50%
Moderate Reduce doxorubicin by 50% and omit docetaxel
Severe Omit doxorubicin and docetaxel
Peripheral neuropathy
Grade 2, which is present at the start of the next cycle Reduce docetaxel by 25%;
If persistent, reduce docetaxel by 50%
Grade 3 or Grade 4 Omit docetaxel
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 docetaxel, doxorubicin and cyclophosphamide by 25%
3rd occurrence: Reduce docetaxel, doxorubicin and cyclophosphamide by 50%
4th occurrence: Withhold chemotherapy
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 docetaxel, doxorubicin and cyclophosphamide by 50%
2nd occurrence: Withhold chemotherapy
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 docetaxel, doxorubicin and cyclophosphamide by 25%
3rd occurrence: Reduce docetaxel, doxorubicin and cyclophosphamide  by 50%
4th occurrence: Withhold chemotherapy
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 docetaxel, doxorubicin and cyclophosphamide  by 50%
2nd occurrence: Withhold chemotherapy

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.

Cyclophosphamide
  Interaction Clinical management
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Increased toxicity of cyclophosphamide possible due to increased conversion to active (and inactive) metabolites Avoid combination or monitor for cyclophosphamide toxicity
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Reduced efficacy of cyclophosphamide possible due to decreased conversion to active (and inactive) metabolites Avoid combination or monitor for decreased clinical response to cyclophosphamide
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs) Additive nephrotoxicity Avoid combination or monitor kidney function closely
Amiodarone Possible additive pulmonary toxicity with high-dose cyclophosphamide (i.e. doses used prior to stem cell transplant; 60 mg/kg daily or 120 to 270 mg/kg over a few days) Avoid combination or monitor closely for pulmonary toxicity
Allopurinol, hydrochlorothiazide, indapamide Delayed effect. Increased risk of bone marrow depression; probably due to reduced clearance of active metabolites of cyclophosphamide Avoid combination, consider alternative antihypertensive therapy or monitor for myelosuppression
Ciclosporin Reduced efficacy of ciclosporin due to reduced serum concentration Monitor ciclosporin levels; adjust dosage as appropriate; monitor response to ciclosporin
Suxamethonium Prolonged apnoea due to marked and persistent inhibition of cholinesterase by cyclophosphamide Alert the anaesthetist if a patient has been treated with cyclophosphamide within ten days of planned general anaesthesia
Docetaxel
  Interaction Clinical management
CYP3A4 and P-gp inhibitors (e.g. amiodarone, aprepitant, azole-antifungals, ritonavir, lapatinib, nilotinib, sorafenib, macrolides, ciclosporin, grapefruit juice etc.) Increased toxicity of docetaxel possible due to reduced clearance Avoid combination or monitor for docetaxel toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John’s wort etc.) Reduced efficacy of docetaxel possible due to increased clearance Avoid combination or monitor for decreased clinical response to docetaxel
Doxorubicin
  Interaction Clinical management
Cardiotoxic drugs (eg. bevacizumab, calcium channel blockers, propranolol, trastuzumab etc.) Increased risk of doxorubicin-induced cardiotoxicity Avoid combination or monitor closely for cardiotoxicity
Cyclophosphamide Sensitises the heart to the cardiotoxic effects of doxorubicin; also, doxorubicin may exacerbate cyclophosphamide induced cystitis Monitor closely for cardiotoxicity and ensure adequate prophylaxis for haemorrhagic cystitis when combination is used
Nephrotoxic drugs (e.g. aminoglycosides, amphotericin, contrast dye, frusemide, NSAIDs etc.) Additive nephrotoxicity Avoid combination or monitor kidney function closely
Glucosamine Reduced efficacy of doxorubicin (due to induction of glucose-regulated stress proteins resulting in decreased expression of topoisomerase II in vitro) The clinical effect of glucosamine taken orally is unknown. Avoid combination or monitor for decreased clinical response to doxorubicin
CYP2D6 inhibitors (e.g. SSRIs (esp. paroxetine), perhexiline, cinacalcet, doxepin, flecainide, quinine, terbinafine, ritonavir etc.) Increased toxicity of doxorubicin possible due to reduced clearance Monitor for doxorubicin toxicity
CYP3A4 inhibitors (e.g. aprepitant, azole antifungals, clarithromycin, erythromycin, grapefruit juice, ritonavir etc.) Increased toxicity of doxorubicin possible due to reduced clearance Monitor for doxorubicin toxicity
CYP3A4 inducers (e.g. carbamazepine, phenytoin, phenobarbitone, rifampicin, St John's wort etc.) Reduced efficacy of doxorubicin possible due to increased clearance Monitor for decreased clinical response to doxorubicin
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 hours

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.

Anti-cancer drug induced neuropathy screening tool prior to each treatment.

Prime IV line(s).

Insert IV cannula or access TIVAD or CVAD.

Pre treatment medication

Verify taxane premedication taken or administer as prescribed.

Verify antiemetics taken or administer as prescribed.

Doxorubicin

Extravasation of a vesicant is a medical emergency. Monitor for signs of extravasation throughout administration.

Administer doxorubicin (vesicant):
  • over 5 to 15 minutes
    • via a minibag OR
    • by IV bolus via a side port of a freely flowing IV infusion
  • flush with ~150 mL of sodium chloride 0.9%.
Potential adverse events:
  • potential for flare reaction during administration of doxorubicin (facial flushing and red streaking along the vein), stop infusion and exclude extravasation before continuing at a slower rate of infusion
  • although rare, cardiac arrhythmias may occur during or immediately after doxorubicin administration, if sudden onset of dyspnoea, palpitations or irregular pulse occurs, stop administration and obtain urgent medical officer review.

Docetaxel

Prior to administration:
  • assess patient for fluid retention or weight gain prior to each cycle
    • notify medical officer of any signs of fluid retention or unexplained weight gain.

The medicines information reference publications stipulate the use of non-PVC containing bags and administration sets. However, this is not consistently recommended in the product information, therefore the decision should be at the discretion of the administering unit.

Administer docetaxel (irritant with vesicant properties):
  • via IV infusion over 60 minutes
  • observe for hypersensitivity reactions
  • flush with ~ 100 mL of sodium chloride 0.9%.

Stop infusion at first sign of reaction:

  • 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.

Cyclophosphamide

Administer cyclophosphamide:
  • via IV infusion over 30 to 60 minutes
  • flush with ~ 50 mL of sodium chloride 0.9%.
Potential adverse events:
  • rapid infusion can cause dizziness, rhinitis, nausea and perioral numbness, if symptoms develop slow infusion rate.

Remove IV cannula and/or deaccess TIVAD or CVAD. 

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

Discharge information

Antiemetics - as/if prescribed.

Dexamethasone tablets - as/if prescribed, with written instructions on how to take them.

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 taxanes.

Read more about premedication for prophylaxis of taxane hypersensitivity reactions
Extravasation, tissue or vein injury

The unintentional instillation or leakage of a drug or substance out of a blood vessel into surrounding tissue. This has the potential to cause damage to affected tissue.

Read more about extravasation management
Flare reaction

Anthracycline flare reaction is caused by a localised allergic reaction. It is characterised by erythematous vein streaking, urticaria and pruritus which may occur during drug administration and is often associated with too rapid an infusion. Extravasation must be ruled out if flare occurs.
Nausea and vomiting

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

Read more about taste and smell changes
Red-orange discolouration of urine

Pink/red/orange discolouration of the urine. This can last for up to 48 hours after some anthracycline drugs.
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
Arthralgia and myalgia

Generalised joint pain or and/or stiffness and muscle aches, often worse upon waking or after long periods of inactivity. Can improve with movement. May be mild or severe, intermittent or constant and accompanied by inflammation. 

Read more about arthralgia and myalgia
Fatigue

Read more about fatigue
Haemorrhagic cystitis

An inflammatory process, characterised by diffuse bladder mucosal inflammation resulting in haemorrhage. Patients are at risk following blood and marrow transplant (BMT) or treatment with cyclophosphamide, ifosfamide and/or radiation therapy.

Read more about haemorrhagic cystitis
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
Diarrhoea

Read more about treatment induced diarrhoea
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
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.
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
Fluid retention syndrome

Fluid retention, including peripheral oedema and weight gain, may occur with docetaxel treatment. The main risk factor for development is cumulative docetaxel dose. Pre-medication with dexamethasone may be used. Fluid retention will slowly resolve after cessation of treatment.

Read more about fluid retention syndrome associated with docetaxel
Radiation recall

Erythematous or inflammatory skin reaction resembling severe sunburn at sites previously treated with radiation therapy can occur with certain anti-cancer drugs. Symptoms include vesiculation, desquamation and ulceration of the skin.

Read more about radiation recall

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
Cognitive changes (chemo fog)

Changes in cognition characterised by memory loss, forgetfulness and feeling vague. This is also referred to as 'chemo brain' or 'chemo fog'.

Read more about cognitive changes (chemo fog) 
Nail changes

Hyperpigmentation, paronychia, onycholysis, splinter haemorrhage, pyogenic granuloma formation, subungual haematoma and subungual hyperkeratosis are some of the nail changes associated with anti-cancer drugs.   

Read more about nail toxicities

Delayed (onset months to years)
Menopausal symptoms

Irregular or absent periods, hot flushes, mood swings, sleep disturbance, night sweats, vaginal dryness, decreased libido and dyspareunia. This is caused by ovarian failure and may be temporary or permanent.
Cardiotoxicity

Anthracyclines are the most frequently implicated anti-cancer drugs associated with cardiotoxicity, which typically manifests as a reduction in left ventricular ejection fraction (LVEF), cardiomyopathy, or symptomatic CHF. Anthracycline induced cardiotoxicity has been categorised into acute, early-onset chronic progressive and late-onset chronic progressive and is usually not reversible. The risk of clinical cardiotoxicity increases with a number of risk factors including higher total cumulative doses. 

Read more about cardiac toxicity associated with anthracyclines

The evidence supporting this protocol is provided by a randomised phase lll trial (TAX 316) by Martin et al2 involving 1491 patients with axillary node-positive breast cancer who were randomised to 6 cycles of TAC (docetaxel, doxorubicin, cyclophosphamide) or FAC ( fluorouracil, doxorubicin, cyclophosphamide) as adjuvant treatment post surgery.

The study enrolled patients between 1997 and 1999 from 20 countries. In total 1480 patients (744 TAC and 736 FAC) received treatment and were included in the safety data. The primary end point was disease free survival (DFS) and the median follow up was 55 months.

TAC patients received ciprofloxacin as supportive care on days 5 to 14 of each treatment cycle. 70% of patients enrolled in this study were ER positive. Randomisation was stratified according to institution and the number of axillary lymph nodes (1 to 3 vs 4 or greater).

Efficacy

The TAX 316 trial showed there was a statistically significant difference in both DFS (HR 0.72, 95% CI 0.59 to 0.88, p=0.001) and OS (HR 0.70, 95% CI 0.53 to 0.91, p=0.008) favouring TAC over FAC. The estimated rates of DFS at five years were 75% with TAC and 68% with FAC and the overall survival estimates at 5 years were 87% with TAC and 81% with FAC.

Survival rates in the two study groups2

© N Engl J Med 2005

Toxicity

TAC is more toxic than FAC chemotherapy. Of the TAC group 36% (268/744) of patients developed serious treatment related adverse events compared with 9.2% (67/736) in the FAC arm. The incidence of grade 3/4 adverse events was also higher with TAC (10.2% vs 4.9%). Overall 91.3% of patients completed 6 cycles of TAC and 96.6% completed FAC. TAC was associated with more frequent febrile neutropenia, infection, long-term amenorrhoea, alopecia, peripheral oedema, neurosensory effects and cardiac failure. No deaths occurred as a result of infection. 3 patients developed secondary haematologic cancers (2 in TAC group and 1 in FAC group).2

Adverse events* 2 TAC (%) FAC (%) p-value
Anaemia 4.3 1.6 0.003
Neutropenia 65.5 49.3 <0.001
Thrombocytopenia 2.0 1.2 0.23
Febrile neutropenia 24.7 2.5 <0.001
Nausea 5.1 9.5 0.001
Stomatitis 7.1 2.0 <0.001

*Grade 3 or 4 adverse events (except febrile neutropenia - all grades) 

The evidence supporting this protocol is provided by a phase III multicentre international randomised trial (GEPARTRIO) involving 2072 patients with early breast cancer. Between September 2002 and August 2005, 2012 patients were included in the study (intent to treat population).3

All patients commenced treatment with two cycles of docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC), on day 1, every 3 weeks. The early responders (n= 1390) were randomised to received a further four or six cycles of TAC. The non responders (n=622) were randomised to a further four cycles of TAC or switch to a combination of vinorelbine 25 mg/m2 on days 1 and 8 plus capecitabine 1000 mg/m2 BD on days 1 to 14, every 3 weeks (NX). No patient received trastuzumab during neo- or adjuvant treatment. Within 21 days after completing chemotherapy and after assessment of the final clinical response patients underwent surgery.3

The primary endpoint was to compare the pCR rates in responders and the clinical response rate in non-responders between the randomised arms. The secondary endpoints were disease free survival (DFS) and overall survival (OS).

Efficacy

At a median follow up of 62 months, DFS was significantly longer in early responders treated with TAC x 8 cycles compared with TAC x 6 cycles (HR, 0.78; 95% CI, 0.62 to 0.97; p=0.026). DFS was also significantly longer in early non-responders treated with TAC-NX than in those receiving TAC x 6 cycles (HR, 0.59; 95% CI, 0.49 to 0.82; p=0.001). There was no significant difference in OS observed in these two groups, though there was a trend toward improved OS in responders receiving TAC x 8 cycles compared with TAC x 6 cycles (HR, 0.76; 95% CI, 0.57 to 1.01; p=0.060).3 As the sample size was calculated to provide adequate power for the primary end point, the study is underpowered for the endpoints of DFS and OS. In addition, although the groups were reasonably balanced in terms of baseline characteristics, there were fewer patients with grade 3 tumours in the non-responder group treated with TAC-NX (25%) compared with TAC x 6 cycles (36%), and this difference was statistically significant. 

Rather than comparing between treatment strategies in the randomised responder vs non-responder groups, the two investigational response-guided arms (TAC x 8 and TAC-NX) were grouped and compared with the conventional therapy arms (TAC x 6). Though this grouping is somewhat counterintuitive, as the intent of the response-guided therapy in responders and non-responders is very different as is the underlying biology, the results suggest that among the hormone receptor-positive patients, DFS was comparable in patients with or without a pCR, but response-guided chemotherapy significantly prolonged DFS compared with conventional chemotherapy. For patients with hormone receptor-negative disease achieving a pCR was associated with longer DFS, but response-guided therapy did not prolong DFS.3

DFS and OS in (A, B) responding, (C, D) non-responding, and (E, F) all patients comparing response-guided with conventional chemotherapy3

© J Clin Oncol 2013

Toxicity

The toxicity data for this protocol has been extrapolated from the adjuvant setting. 

Grade 3/4 adverse events 2 TAC (%)
Anaemia 4.3
Neutropenia 65.5
Thrombocytopenia 2.0
Febrile neutropenia 24.7
Nausea 5.1
Stomatitis 7.1
1
von Minckwitz, G., S. Kummel, A. du Bois, et al. 2008. "Pegfilgrastim +/- ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study." Ann Oncol 19(2):292-298.
2
Martin, M., T. Pienkowski, J. Mackey, et al. 2005. "Adjuvant docetaxel for node-positive breast cancer." N Engl J Med. 352(22):2302-2313.
3
von Minckwitz, G., J. U. Blohmer, S. D. Costa, et al. 2013. "Response-guided neoadjuvant chemotherapy for breast cancer." J Clin Oncol 31(29):3623-3630.

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Version 3

Date Summary of changes
28/08/2024

As per ASCO 2020 and MASCC/ESMO 2023 guidelines and consensus of the breast reference committee, detailed treatment schedule updated as follows:

  • Dexamethasone day 3 and 4 removed.
  • Footnote added "Dexamethasone 4 to 8 mg on day 3 and 4 may be required for those with risk factors for delayed nausea and vomiting."

Version number changed to V.3. 

Version 2

Date Summary of changes
19/07/2023

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.2.
05/12/2023

Protocol reviewed electronically by Medical Oncology Reference Committee. No changes. Next review 4 years.
06/05/2024 Protocol title updated from “Breast adjuvant/neoadjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide)” to “Breast neoadjuvant/adjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide)”.

Version 1

Date Summary of changes
25/08/2022 New multi-indication protocol approved electronically by Medical Oncology reference committee.
30/08/2022 Protocol published on eviQ. Next review in 1 year.
26/10/2022 Treatment schedule updated with missing 'day -1' dexamethasone premedication.

As ID 4114 Breast adjuvant/neoadjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide)​ replaces two existing approved protocols, their individual History sections are included below for consistency in documentation. 

ID 13 Breast adjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide) version 8
Date Summary of changes
4/4/2007 PBS listing updated.
1/8/2007 Patient information updated.
29/7/2009 Reviewed and transferred to eviQ.
28/06/2010 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).
10/12/2010 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.
27/04/2012 Protocol reviewed at Medical Oncology Reference Committee meeting.
No change and next review in 2 years.
20/02/2014 Side effects updated, hyperlacrimation and palmar-plantar erythrodysesthesia added.
09/05/2014 Protocol reviewed by email survey. No change and next review in 2 years.
PHC view removed.
16/02/2016 Discussion with Medical Oncology Reference Committee Chairs and protocol to be reviewed every 5 years. Next review due in 3 years.
31/05/2017 Transferred to new eviQ website. Protocol version number changed to V.3.
Antiemetic change: Netupitant/palonosetron combination has replaced aprepitant and a 5HT3 receptor antagonist in combination with dexamethasone for all highly emetogenic regimens.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.4.
24/01/2019 Treatment schedule updated: dexamethasone dose reduced to daily on day 1 and 2 due to drug interaction with netupitant, note added indicating day 3 and 4 dose may not be required as per Medical Oncology Reference Committee consensus. Version number changed to V.5
08/10/2019 Protocol reviewed at Medical Oncology Reference Committee meeting on 30/08/2019. Clinical information updated with PBS expanded indications for GCSF. Next review in 5 years.
03/02/2020 Order of administration for the drugs in TAC note removed. 
04/05/2020 Clinical information updated- FBC nadir cycle 1 removed from blood tests, wording changed from 'each treatment' to 'each cycle'. Version number changed to V.7
04/09/2020 Biosimilar drug added to clinical information. Version number changed to V.8.
ID 1295 Breast neoadjuvant TAC (DOCEtaxel DOXOrubicin CYCLOPHOSPHamide) version 7
Date Summary of changes
08/04/2016 New protocol taken to Medical Oncology Reference Committee meeting
07/07/2016 Protocol approved and published on eviQ
31/05/2017 Transferred to new eviQ website. Protocol version number changed to V.2.
Antiemetic change: Netupitant/palonosetron combination has replaced aprepitant and a 5HT3 receptor antagonist in combination with dexamethasone for all highly emetogenic regimens.
10/05/2018 Haematological dose modifications updated as per consensus of the expert clinician group. Version number changed to V.3.
30/01/2019 Protocol reviewed electronically by Medical Oncology Reference Committee. Treatment schedule updated: dexamethasone dose reduced to daily on day 1 and 2 due to drug interaction with netupitant, note added indicating day 3 and 4 dose may not be required as per Medical Oncology Reference Committee consensus. Version number changed to V.4. Next review in 5 years.
08/10/2019 Clinical information updated with PBS expanded indications for GCSF. 
03/02/2020 Order of administration for the drugs in TAC note removed. 
04/05/2020 Clinical information updated- FBC nadir cycle 1 removed from blood tests, wording changed from 'each treatment' to 'each cycle'. Approximate treatment time changed to 2.5 hours. Version number changed to V.6.
04/09/2020 Biosimilar drug added to clinical information. Version number changed to V.7.

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https://www.eviq.org.au/p/4114

08 May 2025