Dose-dense AC → paclitaxel

Doxorubicin–cyclophosphamide every 14 days ×4, then paclitaxel every 14 days ×4 (or weekly ×12), with G-CSF support, for early breast cancer

For clinicians and students · Regimen tutorial · Breast cancer · 8 min read · last reviewed September 30, 2026

Key points

ddAC = doxorubicin 60 mg/m² IV push + cyclophosphamide 600 mg/m² IV every 14 days × 4, then paclitaxel 175 mg/m² IV over 3 h every 14 days × 4 (BC Cancer BRAJACTG).
G-CSF is mandatory with every 14-day cycle: filgrastim 5 mcg/kg/day days 2–8 or pegfilgrastim 6 mg on day 2; febrile neutropenia risk exceeds 20% without it.
AC is highly emetogenic: use NK1 antagonist + 5-HT3 antagonist + dexamethasone (± olanzapine per local guidance).
Weekly paclitaxel 80 mg/m² × 12 after AC (BRAJACTW) is an equally preferred taxane schedule and is often better tolerated.
Doxorubicin is cardiotoxic and a vesicant: check baseline cardiac risk and LVEF when indicated, track lifetime anthracycline dose, and give it through a secure line.

Overview

"Dose-dense" chemotherapy gives standard doses more often: every 14 days instead of every 21. The idea is to limit tumour regrowth between cycles. The shorter interval only works because granulocyte colony-stimulating factor (G-CSF) brings back neutrophil counts in time. The regimen has two phases:

four cycles of AC: doxorubicin (an anthracycline, topoisomerase II poison) plus cyclophosphamide (an alkylating agent);
then four cycles of paclitaxel (a microtubule stabilizer).

It is a core anthracycline–taxane backbone for higher-risk early breast cancer, given before surgery (neoadjuvant) or after it (adjuvant).

Indications

Early breast cancer with one or more positive axillary nodes, or node-negative disease at high risk of recurrence (BC Cancer BRAJACTG eligibility), in the adjuvant or neoadjuvant setting.
Triple-negative breast cancer. Anthracycline–taxane chemotherapy is the chemotherapy backbone. Contemporary neoadjuvant regimens for stage II–III TNBC add carboplatin and pembrolizumab, and are separate protocols.
HER2-positive disease. An anthracycline-containing option is AC followed by paclitaxel with trastuzumab (BC Cancer BRAJACTTG). Many centres now prefer anthracycline-free TCHP (see the TCHP tutorial).
Hormone receptor-positive disease. Chemotherapy decisions increasingly rely on genomic risk scores and menopausal status. Endocrine therapy follows chemotherapy.

Exclusions (BC Cancer BRAJACTG): current pregnancy; congestive heart failure (LVEF < 45%) or other significant heart disease; and known hypersensitivity to E. coli-derived products, because G-CSF is produced in E. coli.

Regimen

Source: BC Cancer BRAJACTG.

Phase 1: AC, every 14 days × 4 cycles

Drug	Dose	Route	Day	Notes
Doxorubicin	60 mg/m²	IV push	Day 1	Vesicant: give via a free-flowing line and check for blood return
Cyclophosphamide	600 mg/m²	IV in NS 100–250 mL over 20–60 min	Day 1	Encourage oral fluids
G-CSF	filgrastim 5 mcg/kg/day on days 2–8 (adjust as needed), or pegfilgrastim 6 mg on day 2	SC	Days 2–8 or day 2	Mandatory

Phase 2: paclitaxel, every 14 days × 4 cycles (starting 14 days after the last AC)

Drug	Dose	Route	Day	Notes
Paclitaxel	175 mg/m²	IV in 250–500 mL NS over 3 h	Day 1	Non-DEHP bag and tubing with a 0.2 micron in-line filter
G-CSF	filgrastim 5 mcg/kg/day days 2–8, or pegfilgrastim 6 mg day 2	SC		Mandatory

Total: 8 cycles over 16 weeks.

Filgrastim duration. BC Cancer: reduce the duration if ANC > 10 × 10⁹/L or bone pain is intolerable, but do not stop before the expected nadir. Coverage of G-CSF differs between health systems.

Variants

AC every 14 days → weekly paclitaxel 80 mg/m² × 12. BC Cancer states that weekly paclitaxel for 12 weeks (BRAJACTW) and every-2-week paclitaxel with G-CSF are both preferred taxane deliveries after AC. Patients may switch from BRAJACTG to BRAJACTW for tolerance without special approval. Note that BRAJACTW itself pairs weekly paclitaxel 80 mg/m² × 12 with AC every 21 days.
eviQ (ID 4102). Same AC dose-dense doses (doxorubicin 60 mg/m², cyclophosphamide 600 mg/m², every 14 days × 4) with pegfilgrastim 6 mg SC on day 2. eviQ lists paired protocols with dose-dense (ID 1607) or weekly (ID 4010) paclitaxel.
Sequence reversal. Some centres give the taxane first and AC second, particularly in neoadjuvant TNBC regimens that add carboplatin. Follow the named protocol.

Premedication and supportive care

Antiemetics

AC is highly emetogenic (BC Cancer SCNAUSEA; eviQ "HIGH"). Standard prophylaxis is an NK1 receptor antagonist plus a 5-HT3 antagonist plus dexamethasone. Many guidelines add olanzapine.
eviQ's default is netupitant/palonosetron plus dexamethasone 12 mg on day 1 (may be reduced to 8 mg), with dexamethasone on the following days.
Anticipatory nausea is common by cycle 3–4 if early control is poor. Get cycle 1 right.

Paclitaxel hypersensitivity premedication (BC Cancer, mandatory)

dexamethasone 20 mg IV 45 min before;
diphenhydramine 50 mg IV plus famotidine 20 mg IV 30 min before.
After a prior reaction, rechallenge premedication adds dexamethasone 20 mg PO 12 h and 6 h before treatment.
Paclitaxel itself is of low emetic risk. BC Cancer notes that additional antiemetics are "not usually required".

Growth factor

G-CSF is integral to the schedule, not optional. BC Cancer states that febrile neutropenia risk is greater than 20% without G-CSF.
Warn about bone pain. Acetaminophen, or an antihistamine per local practice, may help.

Other supportive care

Scalp cooling may reduce alopecia where available.
Offer fertility counselling before starting.
Plan contraception: anthracyclines and taxanes are teratogenic.

Key toxicities

Hematologic

Neutropenia is the dose-limiting toxicity. Even with G-CSF, febrile neutropenia is an oncologic emergency.
Anemia accumulates over the 16 weeks.

Doxorubicin

Cardiotoxicity.
Acute: arrhythmia, which is rare.
Chronic: dose-dependent cardiomyopathy that can present years later.
BC Cancer recommends cardiac assessment if the lifetime dose will exceed 450 mg/m². Four cycles at 60 mg/m² = 240 mg/m².
eviQ lists factors that lower the tolerated lifetime dose: older age, prior mediastinal radiation, hypertensive cardiomegaly, and concurrent high-dose cyclophosphamide.
Vesicant. Extravasation can cause severe tissue necrosis. Follow extravasation guidelines; dexrazoxane is used for anthracycline extravasation in many centres.
Alopecia, which is near-universal.
Mucositis.
Red urine for 1–2 days (harmless; warn patients).
Rare secondary acute myeloid leukemia/MDS.

Cyclophosphamide

Nausea.
Hemorrhagic cystitis, which is uncommon at this dose. Encourage fluids and frequent voiding.
Amenorrhea and ovarian insufficiency.
SIADH (rare).

Paclitaxel

Hypersensitivity. Mainly from the Cremophor EL vehicle. Typically occurs in the first minutes of cycles 1–2.
Peripheral sensory neuropathy. Cumulative and dose-limiting.
Arthralgia and myalgia. Occur 2–5 days after the dose.
Alopecia and neutropenia.

Monitoring

Per BC Cancer BRAJACTG:

Baseline: CBC and differential, total bilirubin, ALT. Measure bilirubin and ALT before the first AC cycle and the first paclitaxel cycle.
Before each treatment: CBC and differential.
If clinically indicated: creatinine, and MUGA scan or echocardiogram. Many centres obtain a baseline LVEF in patients with cardiac risk factors or older age.
Clinical, each cycle: temperature and infection history; mucositis; neuropathy (during the paclitaxel phase); and cardiac symptoms.

Dose-modification principles

BC Cancer BRAJACTG, day-1 counts:

ANC (× 10⁹/L)	Platelets (× 10⁹/L)	Action
≥ 1.0	≥ 100	100% dose
< 1.0	≥ 100	Delay 1 week (or longer), then 100% once ANC > 1.0. If on filgrastim, extend it to days 2–11 for the remaining cycles
≥ 1.0	< 100	Delay 1 week, then give 75%
≤ 1.0	< 100	Delay 1 week, then give 75%

Febrile neutropenia: 75% of the dose for the current and subsequent cycles.
Hepatic dysfunction: doxorubicin and paclitaxel need dose modification (see the BC Cancer Drug Manual).
Renal dysfunction: cyclophosphamide may need modification.
Paclitaxel neuropathy: modify or discontinue per the drug manual.
Paclitaxel arthralgia/myalgia not relieved by simple analgesia: BC Cancer notes limited evidence for prednisone 10 mg PO BID for 5 days starting 24 h after paclitaxel, or a short gabapentin schedule.
Paclitaxel hypersensitivity.
Mild (flushing, rash): complete the infusion under supervision.
Moderate: stop; give diphenhydramine 50 mg IV and hydrocortisone 100 mg IV; restart with a stepped rate.
Severe (respiratory distress, angioedema, hypotension): stop, treat, and discontinue paclitaxel. BC Cancer offers nab-paclitaxel (BRAJPN) as an alternative.

Key trials and evidence

CALGB 9741 (Citron, JCO 2003). In node-positive breast cancer, every-2-week scheduling with filgrastim improved disease-free and overall survival compared with every-3-week scheduling. Sequential and concurrent administration performed similarly.
EBCTCG meta-analysis (Lancet 2019). Pooling 26 trials of about 37,000 women, dose-intense chemotherapy (more frequent cycles or sequential full-dose agents) reduced 10-year recurrence and breast cancer mortality without increasing non-breast-cancer deaths.
E1199 (Sparano, NEJM 2008). After AC, weekly paclitaxel (80 mg/m² × 12) outperformed every-3-week paclitaxel for disease-free and overall survival. This supports weekly paclitaxel as the main alternative to dose-dense paclitaxel.

Clinical pearls

G-CSF is part of the prescription. Make sure it is ordered, funded or covered, and that the patient (or nurse) knows how and when to inject it. Pegfilgrastim goes on day 2, at least 24 h after chemotherapy.
Bone pain from G-CSF is common and usually manageable. Proactive counselling prevents unnecessary emergency visits.
Switch the taxane rather than stopping it. If every-2-week paclitaxel causes troublesome neuropathy or myalgia, moving to weekly 80 mg/m² is an accepted change within BC Cancer's framework.
Count the anthracycline lifetime dose. Record prior anthracyclines, such as childhood lymphoma treatment, and chest radiation. These matter decades later.
Hypersensitivity is usually a cycle 1–2 event. Have an anaphylaxis kit, and a nurse at the bedside for the first 10–15 minutes of paclitaxel.
Neutropenic fever education. A temperature ≥ 38 °C needs same-day assessment and empiric antibiotics within an hour of arrival. Give patients a written card to show emergency staff.

Sources

For your patients

Breast cancer (After a Diagnosis, plain language)