Effectiveness of taxanes over anthracyclines in neoadjuvant setting: A systematic-review and meta-analysis

Table 1 Population, intervention, comparison and outcome characteristics of included studies

Study	Accrual	Population	Regimen Comparison	Outcomes
ABDREEN[9], 2002	104	Locally advanced breast cancer patients in which only responders of previous four cycles of CVAP	Anthracycline Arm: CVAP chemotherapy, comprised of cyclophosphamide (C) 1000 mg/m2, doxorubicin (A) 50 mg/m2, vincristine (V) 1.5 mg/m2 (I.V.), and prednisone 40 mg/d p.o. for 5 d; Taxane Arm: 4 cycles of Docetaxel (D) 100 mg/m2 was given as an I.V. infusion over 1 h and repeated at 21-d intervals. In addition, these patients received prednisone 100 mg for 5 d, beginning 24 h prior to docetaxel administration.	pCR1, pCR2, OR, cCR, OS
ACCOG[24], 2010	363	Patients with primary tumour>3 cm, inflammatory or locally advanced non-metastatic breast cancer patients	Anthracycline Arm: Six cycles of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2) both administered every 3 wk (6xAC); Taxane Arm: Six cycles of doxorubicin (50 mg/m2) and docetaxel (75 mg/m2) administered as a 1-h I.V., with both drugs being given every 3 wk (6xAD).	pCR1, pCR2, pCR3, OR, cCR, BCS; Toxicity, OS, DFS, LRR, DM
Amsterdam trial[25], 2005	57	Invasive breast cancer greater than 3 cm and/or at least one tumor-positive auxiliary lymph node	Anthracycline Arm: Six cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 administered every 3 ws (6xAC); Taxane Arm: Six cycles of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (6xAD) 3 wk.	pCR2,
EORCT BIG-01[26], 2011	1856	Invasive breast cancer <71 years with large operable/inflammatory breast cancer patients suitable for neoadjuvant chemotherapy	Anthracycline Arm: Six cycles of iv FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, and cyclophosphamide 500 mg/m2) or tailored FEC (F600, E75, C900) starting on day 1 and then every 21 d with GCF (6xFEC); Taxane Arm: Three cycles of docetaxel 100 mg/m2 iv, followed by 3 cycles of epirubicin 90 mg/m2 and docetaxel 75 mg/m2 on day 1 every 21 d, without GCF.	pCR2, cCR, BCS; Toxicity
NSABP FB-9[8], 2015	50	HER2 negative breast cancer patients with palpable mass of ≥ 2cm in breast or axilla or inflammatory breast cancer patients	Anthracycline Arm: 4 cycles of Eribuline 1.4 mg/m2 on days 1 and 8 of a 21-d cycle followed by A60 C600, every 21 d for 4 cycles; Taxane Arm: Weekly Paclitaxel 80 mg/m2 for 12 doses followed by standard A60C600 every 21 d for 4 cycles.	pCR1, OR, cCR, BCS, Toxicity
Madrid trial[20], 2011	211	Female breast cancer patients aged 18-78 years of clinical stage IIB, IIIA or IIIB and with palpable breast cancer not amenable to BCS	Anthracycline Arm: Four cycles of doxorubicin (75 mg/m2 body surface area); Taxane Arm: Four cycles docetaxel 100 mg/m2 with G-CSF support every 3 wk.	pCR1
Saura et al[4], 2013	295	Breast cancer patients of stage T2-3N0-3M0	Pretreatment: patients received four cycles of doxorubicin (60mg/m2 iv) and cyclophosphamide (600 mg/m2 iv) every 3 wk; Anthracycline Arm: Ixabepilone (40 mg/m2, 3-h infusion) every 3 wk for 4 cycles; Taxane Arm: paclitaxel (80 mg/m2, 1-h infusion) weekly for 12 wk.	pCR1, pCR3, OR, cCR, BCS, Toxicity
NCC Korea[21], 2008	209	Previously untreated stage II/III breast cancer patients with auxiliary lymph node involvement of age ≥ 18 years, ECOG performance status ≤ 1	Anthracycline Arm: doxorubicin 60 mg/m2 IV on day 1 plus cyclophosphamide 600 mg/m2 IV on day 1 every 3 wk for four cycles; Taxane Arm: docetaxel 75 mg/m2 1-h infusion on day 1 plus capecitabine 1000 mg/m2 orally twice daily on days 1-14 every 3 wk for four cycles.	pCR3, OR, cCR, Toxicity, OS, DFS
Norwagian trial[22], 2012	223	Primary stage III breast cancer patients	Anthracycline Arm: 4x Epirubicin 90 mg/m2 administered at 3 wk interval; Taxane Arm: four cycles of paclitaxel 200 mg/m2 administered at 3 wk intervals.	OR, cCR, BCS, OS
Learn et al[27], 2005	144	Invasive breast carcinoma with clinical staging T1c-T3, N0M0 or T1-3, N1M0	Anthracycline Arm: 4 cycles of doxorubicin and cyclophosphamide (A60 C600) every 21 as well as tamoxifen 20 mg per day for 5 yr as NACT; Taxane Arm: 4 cycles of A60 C600 every 21 d further 4 cycles of docetaxel at 100 mg/m2 every 21 d as NACT; Arm 3 (Docetaxel as ACT): 4x AC as ACT (not part of the current study).	pCR1; OR
Diéras et al[5], 2004	240	Breast cancer patients of stage T2-3N0-1M0, who were not assessable for breast conserving surgery	Anthracycline Arm: 4 cycles of A60 C600 i.v. every 21 d; Taxane Arm: doxorubicin 60 mg/m2 as (IV) bolus during 5 to 15 min immediately followed by paclitaxel 200 mg/m2 as a 3-h infusion every 21 d for 4 cycles.	pCR3, OR, cCR, cPR, BCS; Toxicity, OS, DFS, LRR, DM
Tabchy et al[28], 2010	273	Breast cancer patients with clinical stage I to III	Anthracycline Arm: six courses of 5-fluorouracil (500 mg/m2), doxorubicin50/epirubicine100, and cyclophosphamide (500 mg/m2) all on day 1 repeated in 21-d cycles; Taxane Arm: 12 courses of weekly paclitaxel (80 mg/m2/wk) followed four cycles of anthracycline chemotherapy all on day 1 repeated in 21-d cycles.	pCR1; BCS
NSABP-27[6], 2006	2411	Primary operable breast cancer patients with palpable tumor of stage T1c-3, N0-1 M0.	Arm1- 4 cycles of Doxorubicin 60 mg/m2 Cyclophosphamide 600 mg/m2 every 3 wk; Arm 2-Doxorubicin 60 mg/m2 Cyclophosphamide 600 mg/m2 every 3 wk × 4 followed by Docetaxel 100 mg/m2 every 3 wk × 4 followed by surgery; Arm3 (ACT arm)- Doxorubicin 60 mg/m2 Cyclophosphamide 600 mg/m2 every 3 wk × 4 followed by surgey--> Docetaxel 100 mg/m2 every 3 wk × 4	pCR2, pCR3, OR, cCR, BCS; Toxicity, OPS, DFS, LRR, DM
Buzdar et al[23], 1999	174	Invasive, but non-inflammatory, breast cancer with stage II to IIIA disease	Anthracycline Arm: 4 × FAC (fluorouracil 500, cyclophosphamide 500 mg/m2, doxorubicin 50 mg/m2) every 3 wk interval; Taxane Arm: Paclitaxel 250 mg/m2 as a 24-h continuous infusion at 3-wk intervals for four cycles.	pCR3, OR, cCR, BCS; Toxicity, DFS
Cortés-Flores et al[30], 2008	41	Stage IIB and IIIA, locally advanced breast cancer patients	Anthracycline Arm: 5-fluorouracil epirubicine cyclophosphamide; Taxane Arm: docetaxel and epirubicine.	pCR2
Sivasanker et al[29],2017	101	Locally advanced breast cancer patients’ candidates for NACT	Anthracycline Arm: Cyclophosphamide 500 mg/m2, Doxorubicin 50 mg/m2 and 5-FU 500/m2 as IV infusion repeated every 21 d; Taxane Group: Paclitaxel 175 mg/m2 as a 3 h IV infusion, Doxorubicin 50 mg/m2 as IV infusion.	pCR1, pCR2, OR, cCR, BCS

pCR1: Pathological complete response to breast as well as axilla; pCR2: Pathological complete response to breast regardless of axilla; pCR3: Pathological complete response to breast allowing for ductal carcinoma in situ; NACT: Neoadjuvant Chemotherapy; OR: Overall response; cCR: Clinical complete response; BCS: Breast conserving surgery; OS: Overall survival; DFS: Disease free survival; LRR: Loco-regional recurrence; DM: Distant metastasis.