Toremifene in the treatment of breast cancer

Table 1 Randomized controlled clinical trials

Ref.	Type	Pts	Diagnosis	Receptor status	Follow-up	Treatment	Results
Nomura et al[39], 1993	DB	114 women	Advanced or recurrent breast cancer	NS	NS		RR	Time to onset of CR	Duration of efficacy
						TOR 40 mg	26.3%	91 d	155 d
						TAM 20 mg	28.1%	169 d (P < 0.05)	154.5 d
Hayes et al[29], 1995	OL	648 post- or peri-menopausal women	Metastatic breast cancer	Positive or unknown	NS		Overall RR	CR + PR	PFS
						TOR 60 mg	50%	21%	5.6 mo
						TOR 200 mg	48%	23%	5.6 mo
						TAM 20 mg	44% (ns)	19% (ns)	5.8 mo (ns)
Gershanovich et al[31], 1997	OL	463 post-menopausal women	Advanced breast cancer	Positive or unknown	Median 20.5 mo		RR		PFS
						TOR 60 mg	20.4%		49
						TOR 240 mg	28.7%		61
						TAM 40 mg	20.8%		50
Pyrhönen et al[32], 1997	DB	415 post-menopausal women	Advanced breast cancer	Negative or unknown	Median 20.5 mo		CR+PR	TTF	TTP	Median OS
						TOR 60 mg	31.3%	6.3 mo	7.3 mo	33 mo
						TAM 40 mg	37.3%	8.5 mo	10.2 mo	38.7 mo
Holli et al[33], 2000	OL	899 post-menopausal women	Early invasive breast cancer (adjuvant treatment)	Any	Median 3.4 yr		Time to recurrence	Overall recurrence rate	Recurrence rate	Died during follow-up
						TOR 40 mg	21.6 mo	23.1%	20.3%	18.5%
						TAM 20 mg	23.5 mo	26.1%	24.3%	20.7%
Milla-Santos et al[34], 2001	DB	217 women	Advanced breast cancer	Positive	NS		CR (mo)	PR (mo)	SD (mo)	Median TTP (mo)	Median survival (mo)
						TOR 60 mg	12.2	25.4	26.4	11.9	15.4
						TAM 40 mg	8.1	24.3	19.6	9.2 (ns)	12.3 (ns)
Pagani et al[35], 2004	OL	1035 peri- or post- menopausal women	Lymph node positive breast cancer (adjuvant treatment)	ER positive	5.5 yr		5-yr DFS		5-yr OS
						TOR 60 mg	72%		85%
						TAM 40 mg	69%		81%
Zejnalov et al[30], 2006	OL	541 post-menopausal women	Disseminated breast cancer	Positive	NS		CR + PR		Median duration of remission
						TAM 20 mg	25.6% (P < 0.05 compared with three other treatments		9.2 mo
						TOR 60 mg	33.0%		11.3 mo
						TOR 240 mg	41.5%		14.5 mo
						LTZ 2.5 mg	35.4%		13.1 mo
Lewis et al[36], 2010	OL	1813 peri- or post- menopausal women	Stage I or II Early primary invasive breast cancer (adjuvant treatment)	Positive	Median 59 mo		5-Yr DFS
						TOR 60 mg	91.2%
						TAM 20 mg	91.2%
Kimura et al[37], 2012	OL	253 post-menopausal women	Early phase breast cancer (adjuvant treatment)	Positive or unknown	Median 66.5 mo		5-yr survival	Cumulative OS	Cumulative DFS
						TOR 40 mg	97%	97.5%	88.4%
						TAM 20 mg	96.7%	97.3%	90.6%
Yamamoto et al[38], 2013	OL	91 post-menopausal women	Advanced, Non-steroidal aromatase inhibitor resistant in metastatic breast cancer	Positive	Median 16.9 mo		CB	ORR	PFS	OS
						TOR 120 mg	41.3%	10.80%	7.3 mo	32.3 mo
						Exemestane 25 mg	26.7% (ns)	2.2% (ns)	3.7 mo (P = 0.045)	12.9 mo (ns)

DB: Double blind; CR: Complete response; PR: Partial response; SD: Stable disease; LSD: Long stable disease; TOR: Toremifene; TAM: Tamoxifen; DFS: Disease-free survival; OS: Overall survival; (O)RR: (Objective) response rate; CB: Clinical benefit; DFS: Disease-free survival; PFS: Progression-free survival; R: Randomized; OL: Open label; UC: Uncontrolled; RA: Retrospective analysis; CC: Case control; Pr: Prospective; CS: Cohort study; AIU: Aromatase inhibitor; TTP: Time to progression.