Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

Table 1

Table showing the studies using metronomic regimens in breast cancer.

Author	Treatment	N	Patient type	SD	PR	CR	ORR	TTP	CB	PFS	OS
Colleoni, 2002	CP 50 mg qd po; MTX 2.5 mg bd 2 days of 1 week po	63	Metastatic pretreated	-	16%	3%	19.0%	-	31.7%	-	-
Colleoni, 2006	CP 50 mg qd po; MTX 2.5 mg bd on 1st and 4th days po	86	Metastatic, pretreated and untreated	-	17%	3	20.9%	-	41.5%	-	-
Colleoni, 2006	CP 50 mg qd po; MTX 2.5 mg bd on 1st and 4th days po; Thalidomide 200 mg qd po	85	Metastatic, pretreated or untreated	-	8%	3	11.8%	-	41.5%	-	-
Orlando, 2006	MTX 2.5 mg bid on 1st and 2nd or 4th days po; CP 50 mg qd po	153	Metastatic, pretreated or untreated	-	16%	5	-	-	15.7% (12 months )	-	-
Orlando, 2006	CP 50 mg qd po; MTX 2.5 mg bid days 1, 4 q1w; Trastuzumab 6 mg/kg q3w	22	Metastatic, pretreated, HER2 +	46%	18%		-	-	-	6 m
Miscoria, 2012	CP 50 mg qd po; MTX 2.5 mg bid days 1, 4 q1w	62	Metastatic pretreated		-	-	-		-	2.6m	7.1 m
Gebbia, 2012	CP 50 mg qd po	22	Metastatic pretreated; hormone resistant	9%	3%	0%	-	3.8 m	?	-	12.8 m
	vs.	Vs.		Vs.	Vs.	Vs.		Vs.			Vs.
	CP 50 mg qd po with MTX 2.5 mg bid 2 days per week	39		12%	8%	0%		4.2 m			14 m
		Wong, 2010		CP 50 mg qd po; MTX 2.5 mg bid po two days q1w Prednisone 5 mg qd	41	Metastatic, pretreated or untreated		7%			2%	15%	24%	10 w	24%		48 w
Garcia-Saenz, 2008	CP 50 mg qd; MTX 1 mg/kg iv q14d; Bevacizumab 10 mg/kg iv q14d; Trastuzumab (in HER2 +)	22	Metastatic, pretreated, HER2 +/-	32%; (24 w)	32%	-	-	-	63.6%	7.5 m	13.6 m
Mayer, 2012	CP 50 mg qd; MTX 2.5 mg qd 2 days per week; Vandetanib 100 mg / 200 mg / 300 mg qd	20	Metastatic, pretreated or untreated	15%; (24 w)	10%	-	-	-	-	-	-
Perroud, 2013	CP 50 mg qd po; Celecoxib 200 mg bid po	155	!!	3%; (24 w)	1 patient	-	-	14 w	46.7%	24 w (40%)	12 m; (46.7%)
Aurilio, 2012	CP 50 mg qd po; MTX 2.5 mg bd on 1st and 4th days per week po; Fulvestrant 250 mg im q28d	32	Metastatic, pretreated, HR +	!!	!!	!!	!!	!!	56%	-	-
Crivellari, 2013	CP 50 mg qd po; MTX 2.5 mg bd on 1st and 4th days per week po	36	Non-metastatic, >65 y, untreatable, HR-	-	Closed early	-	-	-	-	42 w; (81%)	-
Dellapasque, 2011	CP 50 mg qd po; Liposomal Doxorubicin 20mg/m2	29	Non-metastatic, untreatable, preoperatively	34.5%	62.1%	-	-	-	-	-	-
Soriano, 2011	CP 50 mg qd po; MTX 2.5 mg bid; 1E10-Alum	21	Metastatic,	4%	-	-	-	9.8 m	-	-	12.9 m
Dellapasque, 2008	CP 50 mg qd po; Capecitabine 500 mg tid po; Bevacizumab 10 mg/kg q2w	46	Metastatic	17%	46%	2%		42 w	68%	-	-
Licchetta, 2010	CP 50 mg day 1-21 q28d po; Megestrol acetate 80 mg bid po	29	Metastatic, pretreated,; HR +/-, HER2 +/-				31%	7.4 m			13.4 m
Wang, 2012	CP 65 mg /m2 iv days 1-14 q3w; Capecitabine 1000 mg/m2 bid days 1-14 q3w	68	Metastatic, pretreated	-	-	-	30.3%	5.2 m	53.0%	-	16.9 m
Yoshimoto, 2012	CP 33 mg/m2 bid days 1-14 q3w; Capecitabine 828 mg/m2 bid days 1-14 q3w	51	Metastatic, HER2-; ER-/ER+	13%	-	-	44.4%	-	-	10.7/13.2	1 y (86%); 2 y (71%)
Smith, 2000	5-FU 1 mg/m2 days 1-28 q35d po; Eniluracil 10 mg/m2 days 1-28 q35d po	29	Metastatic	24%; (3 m)	55%
Taguchi, 2010	Capecitabine 825 mg/m2 bid days 1-21 q 28d	33	Metastatic, untreated recurrent	24%; (> 6 m)	-	-	18%	-	-	6.9 m	24.8 m
Fedele, 2012	Capecitabine 1500 mg qd	58	Metastatic, pretreated		2; (pretreated with Standard Capecitabine)	7; (pretreated with Standard Capecitabine)		7 m	62%		17 m
Watanabe, 2009	UFT 300 mg tid		T0, high risk, adjuvant	-	-	-	-	-	-	(RFS) 5 y (87.8 %)	5 y (96.2 %)
Cazzaniga, 2014	Capecitabine 500 mg tid; Vinorelbine 20-30-40 mg/tot	31	Metastatic, pretreated,	-	-	-	-	-	58.1%	-	-
Young, 2012	Capecitabine 1250 mg/m2 qd; Docetaxel 15mg/m2; Celecoxib 200 mg bid	38	Metastatic, pretreated	8%; (6 m)	34%	-	-	3.6 m	42%	-	-
Schwartzberg, 2014	Capecitabine 1500/2000 mg daily in divided doses; Fulvestrant 500 mg day 1, 250 mg day 1, 15, 28 followed by 250 mg q28d	41	Metastatic, HR+, HER2-	-	-	-	-	26.94 m	-	14.98 m	28.65 m
Otsuka, 2015	Irinotecan 60 mg/m2 days 1, 8, 15 q4w; TS-1 80 mg/m2 days 3-7, 10-14, 17-21 q4w	34	Metastatic, recurrent	3%	44%	-	-		-
Alagizy, 2015	Capecitabine 500 mg bid po	41	Operated, neoadjuvant FEC100+, +/- Postoperative RT, HR-, HER2-	-	-	-	-	-	-	-DFS-; 42.4 m	44.34 m; (estimated)
Addeo, 2012	Temozolomide with radiotherapy and following 4 w; Temozolomide 75 mg/m2 days 1-21 q4w; Vinorelbine 70 mg/m2 1,3,5 weekly for 3 w q4w, max 12 cycles	36	Untreated brain metastasis,		44%	8%	52%	-	-	8 m	11 m
Addeo, 2013	Vinorelbine 70 mg/m2 1,3,5 weekly for 3 w q4w, max 12 cycles	34	Metastatic	-	32%	6%	-	-	-	7.7 m	15.9 m
Saloustros, 2011	Vinorelbine 50 mg 3 times per week; Bevacizumab 10 mg/kg 2 times per week q28d	13	Metastatic, pretreated	46%	8%	Closed early	-	-	-	-	-
De Iuliis, 2015	Vinorelbine 30 mg q2d	32	Metastatic		-	-	-	-	50%	-	-
Bottini, 2006	Letrozole 2.5 mg qd	57	HR+,		-	-	71.9%			-	-
	Letrozole 2.5 mg qd and CP 50 mg qd 6 months	57					87.7%
Manso, 2013	NP-Liposomal Doxorubicin 30 mg iv; 5-FU 500 mg iv; Vincristine 0.25 mg iv; CP 50 mg qd po; Prednisone 20 mg	38	Metastatic, pretreated	27%	-	-		281 d		8.4 m	21 m
Masuda, 2014	Paclitaxel 80 mg/m2 days 1. 8. 15, 4 cycles; Cyclophosphamide 50 mg qd po 4 cycles; Capecitabine 1200 mg/m2 qd 4 cycles; 5-FU 500 mg/m2 q3w, 4 cycles; Epirubicin 100 mg/m2 q3w, 4 cycles; CP 500 mg/m2 q3w, 4 cycles	33	HR-, ER-, preoperative	-	54.5%	-	-	-	31; (93.9%)	-	-
Montagna, 2012	Capecitabine 500 mg tid; CP 50 mg qd; Bevacizumab 15mg/kg q3w; Erlotinib 100 mg qd	24	Metastatic, untreated, HR -, HER2-	21%; (9 w)	58%	4%	-	-	75%	43 w	-
Munzone, 2010	P Liposomal-Doxorubicin	45	Metastatic, untreated, pretreated	39%	18%	-	-	-	45%	-	-
Mutlu, 2015	CP 50 mg qd po; Etoposide 50 mg bid 2 days per week	-	Metastatic, pretreated			-	-	-		7.03 m	32.5 m
Taguchi, 2013	Capecitabine 828 mg/m2 bid po days 1-21 q28d; Paclitaxel 80 mg/m2 days 1, 8, 15 q28d	43	Metastatic, pretreated				46.5%			8.3 m	22.9 m
Ambros, 2014	Capecitabine 1000 m2 bid po days 1-14 q21d	86	Metastatic, pretreated, HER2-				24.3%	7 m	55.8%		24.0 m
Neskovic, 1996	Etoposide 50 mg/m2 po days 1-14 q 28d	18	Metastatic, untreated, pretreated		28%	6%
Yuan, 2015	Etoposide 60 mg/m2 po days 1-10 q 21d	75	Metastatic, pretreated	39%	9%					4.5 m