Table 1. Anticancer drugs approved by EMEA from January 1995 to December 2004.

Drug	Year	Indication	Trial design	No. of patients	Primary end points
Docetaxela	1995	ABC, second line, monotherapy	6 SAT	228	RR
Topotecan	1996	AOC, second line	RCT	235	RR
Toremifene	1996	ABC, first line, postmenopausal	3 RCT	648, 415, 463	RR, RR, RR
Doxorubicin pegylatedb	1996	AIDS – Kaposi	SAT	247	RR
			SAT	137	RR
Docetaxel	1997	ABC, second line, with capecitabine	RCT	429	TTP
		ABC, first line, with doxorubicin	RCT	477	TTP
Temozolide	1998	GBM, refractory	RCT, SAT	225, 138	PFS, PFS
		Anaplastic astrocytoma, first line	SAT	162	PFS
Tasonermin	1999	Limbs sarcoma	4 SAT	39,23,23,103	RR, RR, RR, RR
Paclitaxel	1999	AIDS, Kaposi, second line	SAT	107	RR
Docetaxel	1999	A-NSCLC, second line	3 RCT	NA, NA, NA	OS, OS, OS
		A-NSCLC, first line with cis-platinum	RCT	1220	OS
Doxorubicin pegylated	2000	AOC, second line	RCT	474	TTP
Doxorubicin pegylated	2000	ABC, first line, when A nonindicated	2 RCT	509, 301	PFS, PFS
Paclitaxel	2000	ABC, second line or when A nonindicated	NC-RCT	312	TTP
Paclitaxel	2000	ABC, second line	NC-RCT	120	PFS
Trastuzumab	2000	ABC, first line in combination with paclitaxel, when A nonindicated	RCT	469	TTP
		ABC, second line, single agent	SAT	222	RR
Altretinoin	2000	AIDS-Kaposi, after antiretroviral therapy	RCT	238	RR
Capecitabine	2000	A-CRC	2 RCT	605, 602	RR, RR
Capecitabine	2000	ABC, second line with docetaxel	RCT	511	TTP
		ABC, second line, single agent when A nonindicated	SAT	135	RR
Fulvestrand	2001	ABC, postmenopausal, second line	2 RCT	541, 473	TTP, TTP
Imatinib	2002	Adult GIST	NC-RCT	117	RR
Cetuximab	2004	A-CRC, second line, in combination with irinotecan	NC-RCT, 2 SAT	329, 138, 57	RR, RR, RR
Mitotane	2004	Adrenal cortical carcinoma	Review	Review	—

ABC=advanced breast cancer; AOC=advanced ovarian cancer; GBM=gliobastoma multiforme; A-CRC=advanced colorectal cancer; A-NSCLC=advanced non-small-cell lung cancer; GIST=gastrointestinal stromal tumour; A=anthracycline; RCT=randomised clinical trial; SAT=single-arm trial; NC-RCT=noncomparative RCT; OS=overall survival; TTP=time to progression; PFS=progression-free survival; RR=response rate; NA=not available.

^aDocetaxel was first approved under exceptional circumstances on the basis of six pooled SAT, for a total of 228 cases. Later, in 1997, full approval was granted on the basis of two RCT, with 326 and 392 patients and RR as supporting end point.

^bDoxorubicin pegylated was first approved on the basis of SAT. Later, full approval was granted on the basis of two RCT, with 258 and 241 patients and with therapeutic response and response rate, respectively, as supporting end points.