Metronomic chemotherapy for non-metastatic triple negative breast cancer: Selection is the key

Table 2 Neoadjuvant metronomic chemotherapy in triple negative breast cancer

	Ref.	Type of study	n	Patient characteristic	Regimens	pCR	Adverse events
Only MC	Hildebrand et al[34]	Single arm phase II	18	TNBC, ≥ T2	Part 1 (12 wk)	47.60%	Neutropenia G3-G4: 62%
	2016			T4: 5 patients	Weekly DX 24 mg/m2 IV		Febrile neutropenia: 24%
				Node +: 12 patients	Daily CTX 60 mg/m2 PO
				EC II: 47.4%	Followed by Part 2 (12 wk)
				EC III: 28.6%	Weekly PTX 80 mg/m2 IV
					Weekly C 2AUC IV
	Tiley et al[35]	Single arm phase II	17	TNBC, T2-T4, N0-N1	Part 1 (12 wk)	46.60%	Thrombocytopenia G3: 5%
	2012			Median age: 45 yr (25-83) Inflammatory breast cancer: 3	Weekly DX 24 mg/m2 IV		Neutropenia G4: 29%
					Daily CTX 60 mg/m2 PO		Neuropathy G3: 5%
					Followed by Part 2 (12 wk)
					Weekly PTX 80 mg/m2 IV
					Weekly C 2AUC IV
	Ignatova et al[36]	Single arm phase II	40	TNBC cТ2-4, N2-3, M0	Part 1 (9 wk)	60%	Neutropenia G3-4: 22.2%
	2016			Median age: 50 yr (27-69)	Weekly PTX 60 mg/mm2 IV		Mucositis 8.3%
				Histologic grade 3: 33.3%	Weekly C 2AUC IV		Hand-foot syndrome G3: 5.6%
				Ki67 > 20%: 100%	Then followed by Part 2 (9 wk)
					Weekly DX 25 mg/m2 IV
					Daily CTX 50 mg bid PO
					Daily X 500 mg tid PO
Hybrid	Masuda et al[37]	Single arm phase II	40	ER < 10%, T2-T4, N0-N1	Part 1 ( 4 Cycles every 21 d)	47.50%	Neutropenia G3-4: 35%
	2014			Median age 52 yr (33-69)	Day 1, 7, 14 PTX 80 mg/m2 IV		Hand foot syndrome G3-4: 8%
				N1: 40%	Daily CTX 50 mg PO
				ER < 10%: 17.5%	Daily X 1200 mg PO
				EC I: 12.5%	Followed by Part 2 (4 Cycles every 21 d)
				EC II: 77.5%	Day 1 5-FU 500 mg/m2 IV
				EC IIIA: 10%	Day 1 E 100 mg/m2 IV
					Day 1 CTX 500 mg/m2 IV
	Cancello et al[38]	Single arm phase II	34	ER ≤ 10%, PR ≤ 10%, Her2-Median age: 45 yr (31-64)	Part 1 (4 cycles every 21 d)	56%	Neutropenia G3-4: 38%
	2015			Premenopausal: 73%	Day 1 5-FU 200 mg/m2 per day continuous		Anemia G3-4: 3%
				EC II: 35%	Day 1, 2 E 25 mg/m2 IV
				EC III: 67%	Day 1, P 60 mg/m2 IV
				Histologic grade 3: 82%	Followed by Part 2 (three cycles every 28 d)
					Day 1, 7, 14 PTX 90 mg/m2
					Daily CTX 50 mg/d

EC: Clinical stage; ER: Estrogen receptor; DX: Doxorubicin; CTX: Cyclophosphamide; PTX: Paclitaxel; C: Carboplatin; X: Capecitabine; 5-FU: 5-fluoracil; E: Epirubicin; P: Cisplatin; pCR: Pathologic response; TNBC: Triple negative breast cancer; MC: Metronomic chemotherapy.