1624-Breast neoadjuvant D (DOCEtaxel) (part 2 of FEC-D)

This protocol is based on limited evidence; refer to the evidence section of this protocol for more information.

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

Treatment schedule Treatment schedule

Overview
Detail

Cycle 1 to 3

Drug	Dose	Route	Day
DOCEtaxel	100 mg/m² *	IV infusion	1

Frequency:: 21 days

Cycles:: 3 or 4 *(The phase II trials supporting this regimen used 4 cycles of FEC followed by 4 cycles of docetaxel 75 mg/m2. Given that OS and DFS are essentially equivalent whether chemotherapy is given in the adjuvant or neoadjuvant setting, there are arguments for using either 3 to 4 cycles of FEC followed by 3 to 4 cycles of docetaxel. It is the consensus of the reference committee that 3 to 4 cycles of docetaxel 100 mg/m2 be used for part 2 of the FEC-D regimen)

Notes:

This protocol is part 2 of the FEC-D regimen. See the links below to view the overview of the FEC-D regimen and part 1 of the regimen.
- Link to Breast neoadjuvant FEC-D overview
- Link to Breast neoadjuvant FEC (fluorouracil, epirubicin, CYCLOPHOSPHamide) (part 1 of FEC-D)
For patients with HER-2 positive disease, trastuzumab may be given concurrently with docetaxel. Concurrent trastuzumab and an anthracycline has a higher risk of cardiac toxicity and should only be considered in patients with LVEF of 55% or more.
- Link to Breast neoadjuvant trastuzumab three weekly

Drug status:: Docetaxel in on the PBS general schedule

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 3

Day before chemotherapy
Dexamethasone	8 mg (PO)	TWICE a day with or after food

Day 1
Dexamethasone	8 mg (PO)	TWICE a day with or after food
DOCEtaxel	100 mg/m² (IV infusion)	in 250 mL to 500 mL sodium chloride 0.9% over 60 minutes

Day 2
Dexamethasone	8 mg (PO)	TWICE a day with or after food

Frequency:: 21 days

Cycles:: 3 or 4 *(The phase II trials supporting this regimen used 4 cycles of FEC followed by 4 cycles of docetaxel 75 mg/m2. Given that OS and DFS are essentially equivalent whether chemotherapy is given in the adjuvant or neoadjuvant setting, there are arguments for using either 3 to 4 cycles of FEC followed by 3 to 4 cycles of docetaxel. It is the consensus of the reference committee that 3 to 4 cycles of docetaxel 100 mg/m2 be used for part 2 of the FEC-D regimen)

Treatment schedule - Overview

Cycle 1 to 3

Drug	Dose	Route	Day
DOCEtaxel	100 mg/m² *	IV infusion	1

Frequency:: 21 days

Cycles:: 3 or 4 *(The phase II trials supporting this regimen used 4 cycles of FEC followed by 4 cycles of docetaxel 75 mg/m2. Given that OS and DFS are essentially equivalent whether chemotherapy is given in the adjuvant or neoadjuvant setting, there are arguments for using either 3 to 4 cycles of FEC followed by 3 to 4 cycles of docetaxel. It is the consensus of the reference committee that 3 to 4 cycles of docetaxel 100 mg/m2 be used for part 2 of the FEC-D regimen)

Notes:

This protocol is part 2 of the FEC-D regimen. See the links below to view the overview of the FEC-D regimen and part 1 of the regimen.
- Link to Breast neoadjuvant FEC-D overview
- Link to Breast neoadjuvant FEC (fluorouracil, epirubicin, CYCLOPHOSPHamide) (part 1 of FEC-D)
For patients with HER-2 positive disease, trastuzumab may be given concurrently with docetaxel. Concurrent trastuzumab and an anthracycline has a higher risk of cardiac toxicity and should only be considered in patients with LVEF of 55% or more.
- Link to Breast neoadjuvant trastuzumab three weekly

Drug status:: Docetaxel in on the PBS general schedule

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.

Treatment schedule - Detail

Cycle 1 to 3

Day before chemotherapy
Dexamethasone	8 mg (PO)	TWICE a day with or after food

Day 1
Dexamethasone	8 mg (PO)	TWICE a day with or after food
DOCEtaxel	100 mg/m² (IV infusion)	in 250 mL to 500 mL sodium chloride 0.9% over 60 minutes

Day 2
Dexamethasone	8 mg (PO)	TWICE a day with or after food

Frequency:: 21 days

Cycles:: 3 or 4 *(The phase II trials supporting this regimen used 4 cycles of FEC followed by 4 cycles of docetaxel 75 mg/m2. Given that OS and DFS are essentially equivalent whether chemotherapy is given in the adjuvant or neoadjuvant setting, there are arguments for using either 3 to 4 cycles of FEC followed by 3 to 4 cycles of docetaxel. It is the consensus of the reference committee that 3 to 4 cycles of docetaxel 100 mg/m2 be used for part 2 of the FEC-D regimen)

Indications and patient population

Neoadjuvant treatment of operable breast cancer.

Clinical information

Venous access required

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

Hypersensitivity/infusion related reaction

High risk with docetaxel

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.

Emetogenicity LOW

Dexamethasone has been included as both 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.

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.

Dose modifications

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.
Administration of granulocyte colony-stimulating factor (G-CSF +/- antibiotics) is at clinician discretion and local hospital guidelines.

Haematological toxicity
ANC x 10⁹/L (pre-treatment blood test)
0.5 to less than 1.0	Delay treatment until recovery and consider adding G-CSF for subsequent cycles
less than 0.5	Delay treatment until recovery and consider adding G-CSF for subsequent cycles; If patient is already on G-CSF, consider reducing docetaxel by 25% for subsequent cycles
Febrile neutropenia	Delay treatment until recovery and consider adding G-CSF for subsequent cycles; If patient is already on G-CSF, consider reducing docetaxel 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 by 25% for subsequent cycles

Renal impairment
No dose modifications necessary

Hepatic impairment
Hepatic dysfunction
Minimal	Reduce docetaxel by 25%
Mild	Reduce docetaxel by 50%
Moderate/Severe	Omit 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: 1^st occurrence: No dose reduction 2^ndoccurrence: Reduce docetaxel by 25% 3^rdoccurrence: Reduce docetaxel by 50%
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: 1^st occurrence: Reduce docetaxel by 50% 2^ndoccurrence: Omit docetaxel

Interactions

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:

MIMS - interactions tab (includes link to a CYP-450 table) (login required)
Australian Medicines Handbook (AMH) – interactions tab (login required)
Micromedex Drug Interactions (login required)
Cancer Drug Interactions
Cytochrome P450 Drug Interactions

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

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

Administration

Day 1

Approximate treatment time: 90 minutes

Safe handling and waste management

Safe administration

General patient assessment prior to each day of treatment.

Peripheral neuropathy assessment tool

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

Prime IV line(s).

Insert IV cannula or access TIVAD or CICC.

Pre treatment medication

Verify taxane premedication taken or administer as prescribed.

Administer antiemetics if required

Chemotherapy - Time out

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.

Remove IV cannula and/or deaccess TIVAD or CICC.

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

Discharge information

Antiemetics

Antiemetics as prescribed.

Dexamethasone tablets

Dexamethasone tablets with written instructions on how to take them.

Growth factor support

Arrangements for administration if prescribed.

Patient information

Ensure patient receives patient information sheet.

Neoadjuvant chemotherapy (breast cancer) patient information sheet

Ensure patient receives the Chemotherapy before breast cancer surgery (neoadjuvant chemotherapy) patient information sheet.

Side effects

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
Nausea and vomiting	Read more about prevention of treatment induced nausea and vomiting
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
Fatigue	Read more about fatigue
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
Diarrhoea	Read more about treatment induced diarrhoea
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
Ocular changes	Symptoms may include eye pain, blurred vision, blepharitis, uveitis, optic neuritis, tear duct stenosis, conjunctivitis, hyperlacrimation, watery or dry eyes and photophobia.
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
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
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
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

Late (onset weeks to months)
Anaemia	Abnormally low levels of red blood cells (RBCs) or haemoglobin in the blood. Read more about anaemia
Nail changes	Hyperpigmentation, paronychia, onycholysis, splinter haemorrhage, pyogenic granuloma formation, subungal haematoma and subungal hyperkeratosis are some of the nail changes associated with anti-cancer drugs. Read more about nail toxicities
Alopecia - partial	Hair thinning and/or patchy hair loss. 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

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.

Evidence

Results from the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol B-18 trial demonstrated an increased likelihood of Breast Conservation Surgery (BCS) in breast cancer patients treated with a neoadjuvant anthracycline-based regimen.^r Although the B-18 trial did not demonstrate a survival advantage in patients treated with preoperative chemotherapy, it established pathological complete response (pCR) as a prognostic marker for disease-free survival (DFS).

FEC-D has been successfully utilised in the adjuvant setting with eight-year follow-up data showing a 4% absolute benefit in DFS and 5% benefit in OS (Link to the evidence for adjuvant FEC-D).

A search of the literature did not find strong phase III evidence for use of FEC-D in the neoadjuvant setting. Ohno et al^r and von Minckwitz et al^rstudied the efficacy of neoadjuvant (F)EC-D but in varying combinations with capecitabine.

There were three phase II trials directly studying neoadjuvant FEC-D.^r ^r ^r The expert reference panel supported publication of the protocol on the basis of the information summarised below. The Japan Breast Cancer Research Group (JBCRG) 01 trial, published in 2008, was the largest study to date evaluating neoadjuvant chemotherapy in this patient population^r ^r where the Quasi-Pathologic Complete Response (QpCR – no invasive tumour or only focal residual cells) rate was 25%. Within 40 months median follow-up, 3-year DFS was estimated at 98% for patients with QpCR versus those without (89%, HR 0.38 [95% C.I. 0.09 – 0.84]). The overall clinical response rate was 75%. 85% of patients achieved breast conservation. HER-2 status and response to FEC were independent predictors of QpCR. Grade 3/4 neutropaenia was the common adverse event.

In order to achieve a higher pCR with an improved safety profile, the JBCRG-03 trial, published in 2011,^r assessed the efficacy of the reverse sequence of the chemotherapy used in the JBCRG-01 trial, with 4 cycles of docetaxel (75 mg/m² q3w) followed by 4 cycles of 5-fluorouracil 500 mg/m², epirubicin 100 mg/m², and cyclophosphamide 500 mg/m² q3w in patients with early-stage breast cancer. The primary endpoint was the pathological complete response (pCR) rate defined for the breast alone, assessed by a central review committee. Secondary endpoints included clinical response and safety. Of the 132 patients assessable for pathologic response, 23% experienced a pCR and 6% had a near pathological complete response (few remaining cancer cells), resulting in a QpCR of 29%. Clinical response rate following the initial docetaxel regimen was 64%. The overall clinical response rate was 79%. Breast-conserving surgery was performed in 79% of patients. More patients with triple-negative disease experienced a pCR (14/29, 48 %) versus those with other molecular subtypes. The safety profile was acceptable.

Note that all the phase II trials used 4 cycles of FEC and 4 cycles of docetaxel (75 mg/m²). Given that OS and DFS are essentially equivalent whether chemotherapy is given in the adjuvant or neoadjuvant setting, there are arguments for using either the 6 or 8 cycles of FEC-D.

Evidence for the “FEC” portion of the regime is provided by Mouret-Reynier et al,^r where pCR rates were 15-25% depending on classifications.

Evidence for the “D” portion of the regime is provided by the NSABP B-27 trial. The addition of sequential docetaxel to AC doubled the pCR rate and increased the clinical complete response (cCR) rate but did not improve disease free survival (DFS) and overall survival (OS) compared to AC alone. (Link to the evidence for Breast neoadjuvant AC followed by docetaxel).

Source	Study and year published	Supports use	Is the dose and regimen consistent with the protocol?	Comments
Phase III trials	Ohno et al. 2013^r	Yes	No	4 cycles of FEC (5-FU 500 mg/m², epirubicin 100 mg/m² and cyclophosphamide 500 mg/m²,day 1 q3w) followed by 4 cycles of docetaxel 75 mg/m² day 1 q3w +/- capecitabine 1650 mg/m²/day on day 1 to 14
	von Minckwitz. 2010^r	Yes	No	4 cycles of EC (epirubicin 90 mg/m² and cyclophosphamide 600 mg/m², day 1 q3w) followed by 4 cycles of docetaxel 100 mg/m² day 1 q3w alone, in sequence with, or combined with capecitabine 1800 mg/m²/day on day 1 to 14
Phase II trials	Toi et al. 2008^r	Yes	No	4 cycles of FEC (5-FU 500 mg/m², epirubicin 100 mg/m² and cyclophosphamide 500 mg/m², day 1 q3w) followed by 4 cycles of docetaxel 75mg/m² day 1 q3w
	Iwata et al. 2011^r	Yes	No	4 cycles docetaxel 75 mg/m² q3w followed by 4 cycles 5-FU 500 mg/m², epirubicin 100 mg/m² and cyclophosphamide 500 mg/m² q3w in patients with early-stage breast cancer
	Focan et al. 2005^r	Yes	No	4 cycles of FEC 100 followed by 4 cycles of docetaxel
	Yao et al. 2012^r	Yes	No	6 cycles TEC (docetaxel 75 mg/m², epirubicin 75 mg/m² and cyclophosphamide 600 mg/m² + G-CSF), q3w
Observational studies	-	-	-
Case series	-	-	-
Guidelines	Date published/revised	Supports use	Is the dose and regimen consistent with the protocol?	Comments
NCCN	v.1 2014	Yes	N/A
BCCA	-	-	-
CCO	March 2014	Yes	Yes	3 cycles of FEC (5-FU 500 mg/m², epirubicin 100 mg/m² and cyclophosphamide 500 mg/m²,day 1 q3w) followed by 3 cycles of docetaxel 100 mg/m² day 1 q3w

Efficacy

A summary of the evidence supporting the effect of this protocol is below.

	Study	No. of patients	Effect
pCR	Iwata et al^r	135	23%
Overall clinical response	Iwata et al^r	135	Response rate (RR) 79% (complete RR 21%, partial RR 57%)
BCS*	Toi et al^r	198	85%
QpCR**	Iwata et al^r	135	29%

*BCS= Breast conservation surgery
**Quasi-pCR: complete disappearance of invasive carcinoma in the breast or only focal tumour cells remaining in the stroma in the removed breast^r

Toxicity

A summary of the toxicities associated with this protocol are included in the table below. The most clinically significant toxicity for both parts of the treatment was myelosuppression. In the JBCRG-01 trial, G-CSF was administered at investigators' discretion in 10.5%, 8.2% and 9.4% of treatment cycles of FEC (part 1), docetaxel (part 2) and both (part 1 and 2) respectively.^r For non-hematologic toxicities of any grade, rash, sensory neuropathy, oedema, muscle pain and joint pain occurred more frequently during docetaxel treatment than with FEC. Conversely, the frequency of gastrointestinal symptoms, such as nausea, vomiting and anorexia, was higher with FEC.^r

Grade 3/4 toxicity ^r	FEC % (n=198)	Docetaxel % (n=194)	Importance for prescribing
Neutropenia	44	35	Critical
Febrile neutropenia	20	7	Critical
Leukopenia	35	30	Critical
Thrombocytopenia	1	1	Important
Anaemia	1	0	Important
AST/ALT	2	1	Not important
Nausea	6	1	Not important
Vomiting	5	1	Important
Diarrhoea	1	0	Important
Constipation	0	1	Not important
Fatigue	1	1	Not important
Arthralgia/Myalgia	0	1	Important
Neurotoxicity	0	1	Important
Cardiotoxicity	NR	NR	Critical

FEC = fluorouracil, epirubicin, cyclophosphamide; NR = not reported

References References

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History

Version 3

Date	Summary of changes
09/05/2014	New protocol taken to Medical Oncology Reference Committee meeting.
31/05/2014	Approved and published on eviQ.
22/06/2015	Protocol reviewed electronically by Medical Oncology Reference committee. No changes and next review in 2 years.
31/05/2017	Transferred to new eviQ website. Protocol version number changed to V.2.
03/11/2017	Reviewed by Medical Oncology Reference Committee. No changes. Review in 5 years.
10/05/2018	Haematological dose modificaitons updated as per consensus of the expert clinician group. Version number increased to V.3.

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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First approved:: 31 May 2014
Last reviewed:: 3 November 2017
Review due:: 31 December 2022

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/1624

27 Sep 2021