Tominaga T, Adachi I, Sasaki Y, Tabei T, Ikeda T, Takatsuka Y, Toi M, Suwa T, Ohashi Y
Breast Cancer Center, Toyosu Hospital, Showa University School of Medicine, Tokyo, Japan.
Ann Oncol. 2003 Jan;14(1):62-70. doi: 10.1093/annonc/mdg014.
To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer.
One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks.
Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2.
The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.
为比较新一代非甾体芳香化酶抑制剂来曲唑与该类老一代药物盐酸法倔唑的疗效、安全性和耐受性，我们对绝经后晚期乳腺癌女性患者进行了一项随机双盲试验。
157例绝经后晚期乳腺癌女性患者入组，并在日本进行的一项多中心随机双盲试验中被随机分配接受来曲唑或法倔唑治疗。154例符合条件的患者接受来曲唑1.0mg每日一次（n = 77）或法倔唑1.0mg每日两次（n = 77）治疗，最少治疗8周。
来曲唑的总体客观缓解率[完全缓解（CR）+部分缓解（PR）]显著高于法倔唑（分别为31.2%和13.0%；P = 0.011，Fisher精确检验）。接受来曲唑治疗的患者中，定义为CR、PR和疾病稳定（状态无变化超过24周）的临床获益率（50.6%）也高于法倔唑（35.1%）。来曲唑在软组织、骨骼和内脏的主要病灶方面显著优于法倔唑（P = 0.011，分层Mantel-Haenszel检验）。来曲唑组的中位疾病进展时间为211天，法倔唑组为113天，差异无统计学意义（P = 0.175，log-rank检验）。来曲唑在4周内显著降低了外周血中的雌二醇、雌酮和硫酸雌酮水平。法倔唑对这些激素水平的抑制作用不足。接受来曲唑治疗的患者中有35.9%出现药物不良反应，接受法倔唑治疗的患者中有39.5%出现药物不良反应，两组之间差异无统计学意义（P = 0.74，Fisher精确检验）。大多数药物不良反应的分级为1级或2级。
结果显示，每日一次服用1.0mg来曲唑治疗绝经后晚期乳腺癌女性患者比每日两次服用1.0mg法倔唑更有效，且安全性和耐受性相似。
