Toremifene versus tamoxifen for advanced breast cancer.
BACKGROUND
Toremifene (TOR) and tamoxifen (TAM) can both be used as treatments for advanced breast cancer.


OBJECTIVE
To compare the efficacy and safety of TOR with TAM in patients with advanced breast cancer.


METHODS
The Cochrane Breast Cancer Group's Specialised Register was searched (1 July 2011) using the codes for "toremifene", "fareston", "tamoxifen, "nolvadex, and "breast cancer". We also searched MEDLINE (via PubMed) (from inception to 1 July 2011), EMBASE (via Ovid) (from inception to 1 July 2011), The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2011), and the WHO International Clinical Trials Registry Platform search portal (1 July 2011). In addition, we screened the reference lists of relevant trials or reviews.


METHODS
Randomised controlled trials (RCTs) that compared the efficacy and safety, or both of TOR with TAM in women with advanced breast cancer. Trials that provided sufficient data on one of the following items: objective response rate (ORR), time to progression (TTP), overall survival (OS), and adverse events, were considered eligible for inclusion.


METHODS
Studies were assessed for eligibility and quality. Two review authors independently extracted the following details: first author, publication year, country, years of follow-up, treatment arms, intention-to-treat (ITT) population size, menopausal status of patients, hormone receptor status, response criteria, efficacy and safety outcomes of TOR and TAM arms. Hazard ratios (HR) were derived for time-to-event outcomes, where possible, and response and adverse events were analysed as dichotomous variables. We used a fixed-effect model for meta-analysis unless there was significant between-study heterogeneity.


RESULTS
A total of 2061 patients from seven RCTs were included for final analysis, with 1226 patients in the TOR group and 835 patients in the TAM group. The ORR for the TOR group was 25.8% (316/1226) whereas, the ORR for the TAM group was 26.9% (225/835). The pooled risk ratio (RR) suggested that the ORRs were not statistically different between the two groups (RR 1.02, 95% confidence interval (CI) 0.88 to 1.18, P = 0.83). The median TTP was 6.1 months for the TOR group and 5.8 months for the TAM group. The median OS was 27.8 months for the TOR group and 27.6 months for the TAM group. There were no significant differences in TTP and OS between the two therapeutic groups (for TTP: HR 1.08, 95% CI 0.94 to 1.24; for OS: HR 1.02, 95% CI 0.86 to 1.20). The frequencies of most adverse events were also similar in the two groups, while headache seemed to occur less in the TOR group than in the TAM group (RR 0.14, 95% CI 0.03 to 0.74, P = 0.02). There was no significant heterogeneity between studies in most of the above meta-analyses. Sensitivity analysis did not alter the results.


CONCLUSIONS
TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.
Division of Epidemiology, School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, China.
Chen
C
Mao
Zu-Yao
ZY
Yang
Ben-Fu
BF
He
Shan
S
Liu
Jun-Hua
JH
Zhou
Rong-Cheng
RC
Luo
Qing
Q
Chen
Jin Ling
JL
Tang
D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D013629:Tamoxifen / Q000009:adverse effects / Q000627:therapeutic use*; D017312:Toremifene / Q000009:adverse effects / Q000627:therapeutic use*
D018931:Antineoplastic Agents, Hormonal; D013629:Tamoxifen; D017312:Toremifene