瑞宁得治疗绝经后妇女晚期乳腺癌临床研究

目的 研究瑞宁得（ａｎａｓｔｒｏｚｏｌｅ）治疗绝经后妇女晚期乳腺癌的临床疗效和不良反应。方法 采用多中心开放非随机自身对照方法,６１例绝经妇女晚期乳腺癌患者口服瑞宁得每日１次,每次１ｍｇ连服４－６周,疗前２周内及治疗４周后的３天内检测血中雌二醇（Ｅ２）水平,同时评价疗效和不良反应。结果 ６０例可评价疗效和不良反应,部分缓解（ＰＲ）１３例,好转（ＭＲ）２例,缓解率２１．７％,有效率２５．０％,绝经时     

多西他赛联合卡培他滨治疗复发转移乳腺癌的疗效及相关因素研究

目的　探讨低剂量多西他赛联合卡培他滨治疗复发转移乳腺癌的疗效及其预测因素。方法　２００６年６月至２００９年１２月收治３８例复发转移乳腺癌女性患者给予多西他赛联合卡培他滨治疗,具体方案为：多西他赛６０ｍｇ／ｍ２静滴,ｄ１;卡培他滨９５０ｍｇ／ｍ２口服,每日２次,ｄ１～ｄ１４;２１天为１周期。２个周期评价疗效,并随访无进展生存时间（ＰＦＳ）。选取ＰＳ评分、绝经状态、ＥＲ、ＨＥＲ ２、转移数目、既往化疗共６个指标分别建立两分类Ｌｏｇｉｓｔｉｃ回归模型和Ｃｏｘ风险比例模型,分析上述指标对疗效的预测情况。结果　３８例患者均接受２～６个周期化疗,获ＣＲ３例,ＰＲ１８例,ＳＤ１０例,ＰＤ７例,有效率（ＲＲ）为５５.３％（２１／３８）;中位ＰＦＳ为７.１个月（９５％ＣＩ：４.８～９.６个月）。主要毒副反应为恶心呕吐、乏力、白细胞减少和手足综合征等,其中３～４级白细胞减少为１５.８％。６个指标中ＰＳ评分（Ｐ＝０.００３）、绝经状态（Ｐ＝０.０４３）和转移数目（Ｐ＝０.０２１）均与ＲＲ有关,仅ＰＳ评分为ＲＲ的独立预测因素（Ｐ＜０.０５）;Ｃｏｘ风险比例模型显示,ＰＳ评分是ＰＦＳ的独立预测因素（Ｐ＜０.０５）。结论　低剂量多西他赛联合卡培他滨治疗复发转移乳腺癌的疗效好,安全性高;ＰＳ评分可以作为该方案疗效预测的独立因素。     

卡莫氟联合三维适形放射治疗食管癌的临床研究

目的：研究卡莫氟联合三维适形放射治疗食管癌过程中患者对卡莫氟的耐受性、耐受剂量以及毒副反应与剂量的关系。方法：自２００５年１月～２００６年７月共有６４例食管癌患者,其中４例因卡莫氟的副反应停用,可评价患者６０例。放疗采用三维适形放射治疗。第一剂量组（１４例）卡莫氟１５０ｍｇ／次,每日口服３次;第二剂量组（５０例）卡莫氟２００ｍｇ／次,每日口服３次,放疗全程连续服用。结果：主要的毒副反应为食管炎、血液学毒性和皮肤反应,患者均能耐受。全组ＣＲ８例（１３.３％）,ＰＲ３９例（６５.０％）,ＳＤ９例（１５.０％）,ＰＤ４例（６.７％）,有效率７８.３％（４７／６０）。中位生存时间为１６个月,２年生存率为３０.７％。结论：卡莫氟联合三维适形放射治疗食管癌,采用卡莫氟剂量２００ｍｇ／次、每日３次口服,患者可以耐受。     

小剂量阿糖胞苷和维甲酸治疗高危MDS25例疗效观察

目的：研究高危ＭＤＳ的治疗方法,观察小剂量阿糖胞苷（ＬＤ－Ａｒａ－ｃ）和全反式维甲酸（ＡＴＲＡ）诱导治疗高危ＭＤＳ的疗效。方法：高危ＭＤＳ２５例,应用ＬＤ－Ａｒａ－ｃ１０－１５ｍｇ／ｍ＾２,每１２小时１次皮下注射,２１天一疗程,间隔１０天～１５天重复;ＡＴＲＡ３０～６０ｍｇ／ｄ,分３次口服。结果：完全缓解９例（３６％）,部分缓解４例（１６％）,４例进步,８例无效,总有效率５２％;１０例（４０％）在     

长春地辛,异环磷酰胺和顺铂联合治疗晚期肺癌20例近期疗效观察

目的观察长春地辛、异环磷酰胺和顺铂联合治疗晚期肺癌患者疗效和毒性。方法符合化疗条件的２０例晚期肺癌患者,均完成２周期以上的化疗。方案组成：ＶＤＳ３ｍｇ／ｍ２静注第１、８天,ＩＦＯ２ｇ／日静滴,第１－５天,ｍｅｓｎａ４００ｍｇ静滴,每８小时１次,ＤＤＰ３０ｍｇ／ｍ２第２－４天或８０ｍｇ／ｍ２,第１天,２１－２８天为一周期,完成二周期后评价疗效。结果有效率７５％（１５／２０）,完全缓解率１５％（３／２０）,部分缓解率６０％（１２／２０）,其中小细胞肺癌有效率８３．３％（５／６）非小细胞肺癌７１．４％（１０／１４）。常见毒副反应是白细胞减少Ⅲ度－Ⅳ度,占８５％,其次恶心、呕吐Ⅲ度占２５％。结论该方案对晚期肺癌是疗效较高方案,有条件者可作为一线方案应用。     

帕米膦酸二钠治疗恶性肿瘤骨转移性疼痛24例疗效观察

目的 观察帕米膦酸二钠（ＡＰＤ）治疗恶性肿瘤骨转移性疼痛的疗效。方法 ２４例均应用帕米膦酸二钠治疗，首次６０ｍｇ加入生理盐水５００ｍｌ静滴，３￣４小时滴完，每２周重复３０ｍｇ，共重复２次，总量２０ｍｇ。结果 总有效率（ＣＲ＋ＰＲ）为８３．３％，总完全缓解率（ＣＲ）为５８．３％。对１级、２级、３级疼痛的有效率分别为１００％，６６．７％，３３．３％．完全缓解率分别为８０．０％，３３．３％，结论 ＡＰＤ     

支气管动脉灌注加外照射治疗中晚期肺癌的疗效观察（附36例报告）

目的 探讨同时应用支气管动脉灌注化疗和外放射治疗两种疗法治疗中晚期肺癌的疗效。方法 采用Ｓｅｌｄｉｎｇｅｒ’技术,经支气管动脉灌注化疗药物：顺铂８０ｍｇ,阿霉素５０ｍｇ,丝裂霉素１０ｍｇ或５－氯脲嘧啶１０００ｍｇ,每３～４周灌注一次,３～４次周灌注一次,３～４次为一疗程,放疗于灌注后１０～１５天进行。放射源为＾６０Ｃｏ,所有病例均行对穿照射。剂量ＤＴ２００ｃＧｙ／次,５次／周,总量ＤＴ５０００～６０００ｃＧｙ／２５～３０次,共５～６周。结果 ＣＲ８例（２２．２％）,ＰＲ２３例（６３．６％）,Ｓ３例（８．６％）,Ｐ２例（５．６５％）。总有效率ＣＲ＋ＰＲ为８５．６％,２年生存率２７．８％。结论 支气管动脉灌注加外照射治疗肺癌的协同作用,是目前治疗中晚期肺癌的一种安全、有效的方法。     

甘利欣治疗抗肿瘤药物性肝损害疗效观察

目的 搪塞保肝新药甘利欣对抗肿瘤药后所致的肝损害治疗效果。方法 治疗组３７例，对照组２６例。治疗组用甘利欣１５０ｍｇ稀释于１０％葡萄精溶液５００ｍｌ中一且用普通胰饥素８ｕ、１０％氯化钾１０ｍｌ稀释于１０％葡萄糖溶液５００ｍｌ中静滴。两组均为每日一次，和１０天为一疗程结果 治疗组总有效率９７．３％，对照组总有效率为７７６．９％，疗效差异显著。结论肝利欣治疗抗肿瘤经物性肝损害疗效好，肝细胞损害恢复快。     

戈舍瑞林联合阿那曲唑作为一线内分泌方案治疗绝经前伴中、高危复发转移因素乳腺癌的临床研究

背景与目的:现已证实治疗绝经前乳腺癌患者,阿那曲唑疗效优于他莫昔芬,并有研究表明戈舍瑞林为安全有效的卵巢去势药物,然而两者联用作为乳腺癌内分泌治疗一线方案则鲜有报道.本研究旨在观察分析戈舍瑞林联合阿那曲唑作为绝经前伴中、高危复发转移因素的乳腺癌一线内分泌治疗临床疗效和预后.方法:分析本中心2002年至今应用戈舍瑞林联合阿那曲唑作为绝经前伴中、高危复发转移因素的68例乳腺癌患者一线内分泌治疗方案的疗效和预后:应用戈舍瑞林3.6 mg,每28 d皮下注射1次;阿那曲唑1 mg口服,每天1次;28 d为1个周期.所有患者按期评价疗效和不良反应.结果:68例患者中2例出现肿瘤复发转移,其余66例患者随访至今未出现肿瘤复发转移;中位治疗时间为3.6年,中位随访时间为48个月,无病生存率(disease-free survival,DFS)为97.1%,总生存率(overall survival,OS)为98.5%.结论:戈舍瑞林联合阿那曲唑治疗绝经前伴有中、高危复发转移因素乳腺癌疗效肯定,不良反应较轻,是一种有效的一线内分泌治疗药物.     

卡铂,阿霉素,环磷酰胺联合治疗晚期乳腺癌的临床疗效

作者采用ＣＡＣ方案（卡铂十阿霉素十环磷酰胺）治疗晚期乳腺癌２７例，其中１８例（包括辅助化疗８例）为初治。２０例病人有２处以上转移。卡铂３００ｍｇ／ｍ￣２，静滴，ｄ＿１或１５０ｍｇ／ｍ￣２，ｄ＿（１、２）；阿霉素４０ｍｇ／ｍ￣２，静冲，ｄ＿３；环磷酰胺５００ｍｇ／ｍ￣２，静冲，ｄ＿（３、１０）。２８天为一周期。总有效率６３％（１７／２７），其中完全缓解５例（１８％），部分缓解１２例（４４％），中位缓解期９个月，中位生存期１７个月。对软组织转移有效率为６１％（１１／１８），肺转移为３／５，肝转移和胸膜转移分别为３／３和４／４，骨转移为１／１０。初治者有效率７２％（１３／１８），复治者４／９。本组胃肠反应不重；未发现肾毒性；白细胞减少（Ⅱ、Ⅲ度）占８９％。作者认为，ＣＡＣ方案是治疗晚期乳腺癌的有效方案。     

Phase III Randomized Trial of Toremifene vs Tamoxifen in Hormonodependant Advanced Breast Cancer

Purpose. Efficacy and safety of toremifene (TOR) 60mgs/dayly/o.r. was compared with tamoxifen (TAM) 40mgs/dayly/o.r. in a group of postmenopausal women with advanced breast cancer, without previous systemic therapy for advanced breast cancer. Material and methods. The study was a prospective double-blind randomized trial. All treated patients presented with positive estrogen receptors. Main end points were response rates, toxicity profile analysis, time to progression and survival. WHO and ECOG criteria were employed for response evaluation while toxicity was assesed according to WHO guidelines. Curves were constructed by means of Kaplan–Meier methodology and were compared by means of log-rank test. Results. From January 1996 to January 1999 a total of 217 patients were included in the study (106 in the TOR branch and 111 in the TAM arm). Both groups of patients were homogeneous regarding the main prognostic factors. A response rate of 64% (68/106) was observed in the TOR group as compared with a 52% (58/111) in the TAM group. Median times to progression and overall survival were not significantly different. A lower incidence of undesirable effects was apreciated in the TOR arm. Conclusions. Our data suggest that TOR is an efficient and well-tolerated agent for the therapy of postmenopausal women with hormonal positive receptors advanced breast cancer, and must be considered an alternative to TAM as first line therapy for ER+ advanced breast cancer patients and as well as an adjuvant treatment.     

Meta-analysis of trials comparing toremifene with tamoxifen and factors predicting outcome of antiestrogen therapy in postmenopausal women with breast cancer

Meta-analysis of all clinical data was conducted to compare toremifene 40-60 mg/day (TOR) with tamoxifen 20-40 mg/day (TAM) in postmenopausal women with estrogen receptor (ER) positive or ER unknown advanced breast cancer and assess factors predicting treatment outcome. Data from five randomized parallel group studies (all studies) were combined. Efficacy variables were the response rate in all studies and also the time to treatment failure and survival in the three major studies (pivotal studies). Of the 1421 patients, 725 received TOR and 696 TAM. Response rates were 24.0% and 25.3%, respectively (p = 0.675) with 95% confidence interval (95% CI) for the difference -5.3 to 3.4. Of the 1157 patients in the pivotal studies, 75% had progressed and 50% expired. Median treatment times were 4.9 months in TOR and 5.3 months in TAM groups (p = 0.762, hazard ratio 0.98 with 95% CI 0.87-1.11). Median survival times were 31.0 (TOR) and 33.1 (TAM) months (p = 0.758, hazard ratio 0.98 with 95% CI 0.83-1.15). All results are consistent with the criteria of statistical equivalence between TOR and TAM. More patients in TAM (20%) than in TOR (14%, p = 0.007) discontinued the treatment prematurely but overall the treatments were well tolerated. As the treatments were equally effective all data were analyzed together for predictive factors. High tumor ER concentration, long disease free time, soft tissue metastases, few metastatic sites, and good performance status all independently predicted longer survival (p<0.001). Previous adjuvant tamoxifen predicted shorter survival (p = 0.008). Objective response to treatment or disease stabilization for at least 12 months both predicted prolonged survival (p = 0.001). TOR 60 mg/day and TAM are equally effective and well tolerated in the treatment of advanced breast cancer in postmenopausal women. Probability of survival may be predicted based on patient characteristics and on the initial response to the treatment.     

Toremifene and tamoxifen in advanced breast cancer - a double-blind cross-over trial

Summary Toremifene (TOR) is a triphenylethylene derivative related to tamoxifen (TAM). TOR has antitumor activity, not dependent on estrogen receptors, and responses with TOR have been observed in patients with progressive disease during TAM-treatment. To elucidate possible cross-resistance between these two antiestrogens, we compared their anti-tumor activity in a randomized, double-blind, cross-over study.66 postmenopausal women with advanced estrogen receptor positive or unknown breast cancer and a median age of 63 years (range 38-82) were included. Patients were randomized to TAM 40mg/day or TOR 240mg/day. Treatment continued until progressive disease, when cross-over to the alternative treatment was done. The response rate with first line TOR was 29% (95% confidence limits 10–41%) and with TAM 42% (95% confidence limits 25–61%). Response rates and response durations, survival and toxicity were not significantly different between the two treatments. 44 patients progressing on first line TAM or TOR were evaluable for second line TOR or TAM treatment. As no responses were observed, the possibility of overlooking a response rate of 20% or more is less than 1%.In conclusion, this study strongly indicates that TOR and TAM are clinically cross-resistant in patients with advanced breast cancer.     

Comparison of toremifene and tamoxifen in post-menopausal patients with advanced breast cancer: a randomized double-blind, the 'nordic' phase III study.

The study was planned to compare, in a prospective double-blind randomized trial, the efficacy and safety of toremifene (TOR) and tamoxifen (TAM) in post-menopausal patients with advanced breast cancer who have not had prior systemic therapy for advanced disease. Four hundred and fifteen post-menopausal patients with oestrogen receptor (ER)-positive or ER-unknown advanced breast cancer were randomly assigned to receive daily either 60 mg TOR or 40 mg TAM. The patients were stratified to measurable and non-measurable but evaluable groups. They were assessed for response to therapy, time to progression (TTP), time to treatment failure (TTF), response duration, overall survival and drug toxicity. Two hundred and fourteen patients were randomized into TOR and 201 into TAM treatment. The response rate (complete + partial) was 31.3% for TOR and 37.3% for TAM (P = 0.215). The 95% confidence interval (CI) for the 6% difference was -15.1% to 3.1%. The median TTP was 7.3 months for TOR and 10.2 months for TAM (P = 0.047). The 95% CI for the hazard ratio of 0.80 was 0.64-1.00. A percentage of the TOR patients (9.8%) and the TAM patients (18.9%) discontinued the treatment prematurely (P = 0.011) for various reasons. Consequently, the median TTF of 6.3 vs 8.5 months did not differ significantly (P = 0.271). The hazard ratio was 0.89 and the subsequent 95% CI 0.73-1.09. The median overall survival was 33.0 months for TOR and 38.7 months for TAM (P = 0.645). The hazard ratio was 0.94 with 95% CI of 0.73-1.22. The transient difference in TTP may be related to an imbalance in ER content of the tumours. When only patients with ER-positive tumours were considered (n = 238), no difference between two treatments was seen (P = 0.578). TAM was associated with an overall slightly higher frequency of adverse drug reactions than TOR (44.3 vs 39.3%) and a higher discontinuation rate due to these events (3.5% vs 0.9%). Treatment-emerged moderate dizziness (P = 0.026) and cataracts (P = 0.026) were more frequent among TAM than among TOR patients. In conclusion, TOR (60 mg day(-1)) and TAM (40 mg day(-1)) are equally effective and safe in the treatment of advanced post-menopausal ER-positive or ER-unknown breast cancer.     

Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest Oncology Group study.

PURPOSE: Southwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients. METHODS: Receptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival. RESULTS: Multivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete response [CR], partial response [PR], or stable disease [SD] for greater than 6 months) in this trial was 54%. Response rates to tamoxifen were 43%, 53%, and 61% in subsets of patients with less than 10, 10 to 99, and more than 100 fmol/mg PgR, respectively. Exploratory subset analysis using PgR and other prognostic variables identified ER-positive patient subsets with response rates to tamoxifen ranging from 24% (premenopausal patients) to 86% (postmenopausal patients with ER greater than 38 and PgR greater than 329 fmol/mg). No groups of ER-positive patients were identified who had such a low response rate as to absolutely preclude considering the use of tamoxifen. Multivariate analysis showed the independent, statistically significant predictors were: for response to tamoxifen, menopausal status, PgR, and ER; for time to treatment failure, menopausal status, disease-free interval (DFI), PgR, and ER; and for overall survival DFI, PgR, ER, site of disease, and history of adjuvant therapy. CONCLUSION: We conclude that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.     

依西美坦治疗绝经后晚期乳腺癌的临床研究

目的　观察依西美坦 (优可依 )治疗绝经后晚期乳腺癌的疗效和不良反应。方法　 173例晚期乳腺癌患者进入研究 ,2例因自然绝经不足 1年而被剔除 ,故可评价疗效者 171例 ,可评价不良反应者 173例。患者口服依西美坦 2 5mg,每天 1次 ,连续 4周为 1周期。结果　可评价疗效的 171例患者中 ,完全缓解 (CR) 4例 (2 .3% ) ,部分缓解 (PR) 4 0例 (2 3.4 % ) ,总有效率 (CR +PR) 2 5 .7% ;病情稳定 (SD) 90例 (5 2 .6 % ) ,临床获益 6 9例 (40 .4 % ) ,病情进展 (PD) 37例 (2 1.6 % )。依西美坦对初治患者的有效率为 33.8% (2 5 / 74 ) ,复治患者为 18.1% (17/ 94 ) ,两者差异有显著性 (P =0 .0 197)。对不同转移部位的有效率依次为 :软组织 32 .8% (40 / 12 2 )、骨 2 3.9% (11/ 4 6 )、内脏 12 .4 % (11/ 89) ,三者之间差异有显著性 (P =0 .0 0 2 )。依西美坦的有效率在不同的年龄、绝经时间、无病间期和受体来源于不同阶段病情的患者中 ,差异均无显著性 (P >0 .0 5 )。可评价不良反应的 173例患者中 ,胃部不适 31例(17.9% ) ,乏力 31例 (17.9% ) ,恶心 2 4例 (13.9% ) ,面部潮热 19例 (11.0 % ) ,烦躁 10例 (5 .8% ) ,其他反应及实验室指标异常的发生率均 <5 %。结论　依西美坦能有效治疗绝经后晚期乳腺癌 ,药     

A phase III comparison of two toremifene doses to tamoxifen in postmenopausal women with advanced breast cancer

Efficacy and safety of toremifene 60 and 240mg daily (TOR60 and TOR240) are compared to40 mg tamoxifen daily (TAM40) in postmenopausal womenwith advanced estrogen receptor (ER) positive or ERunknown breast cancer. The study is randomized andopen label in three parallel groups. Primary efficacyvariables are response rate and time to progression.WHO and ECOG criteria were used for measurableand nonmeasurable disease assessment, respectively. Safety was reportedaccording to WHO criteria. Altogether 463 patients wererandomized (157 to TOR60, 157 to TOR240, and149 to TAM40). By data cut-off, after 20.5months median follow-up time, over 70% of thepatients had experienced disease progression. Response rates are20.4%, 28.7%, and 20.8% in TOR60, TOR240, andTAM40, respectively. TOR60 and TAM40 show statistically equivalentefficacy and the difference between TOR240 and TAM40is not significant (P=0.112). Median timesto progression are 4.9 (TOR60), 6.1 (TOR240), and5.0 (TAM40) months and the corresponding hazard ratios(TAM:TOR) 1.015 and 1.124. Again, TOR60 and TAM40are statistically equivalent and the difference between TOR240and TAM40 is not significant (P=0.374).All treatments were well tolerated. As a conclusion,TOR60 and TAM40 show equivalent clinical efficacy andtolerability. The higher dose of toremifene slightly butnot statistically significantly improves response rate and timeto progression. In postmenopausal women, toremifene 60 mgdaily is an effective and safe treatment ofadvanced ER-positive or ER-unknown breast cancer.     

Secondline Chemotherapy Versus Best Supportive Care in Patient with Malignant Pleural Mesothelioma: A Retrospective Study

Introduction: Mesothelioma is a rare neoplasm arising from mesothelial surfaces with the malignant pleuralmesothelioma (MPM) as the most common form. Secondline chemotherapy in MPM is still controversial andin this study we evaluated whether it is superior to best supportive care. Materials and Methods: A total of 51patients with MPM from Acibadem Kayseri Hospital, Kayseri Training and Research Hospital and ErciyesUniversity were analyzed retrospectively. The patients treated with secondline chemotherapies (SLCT) werecompared with those treated with best supportive care (BSC) for overall survival. Results: The median overallsurvival (OS) for firstline chemotherapygSLCT and firstline chemotherapygBSC groups were 20.3 and 14.7months respectively (p=0.079). After firstline chemotherapy the median OS for SLCT and BSC were 5.9 and4.7 months (p=0.355). Discussion: Although there was a trend for improvement in overall survival in patientstreated with secondline chemotherapy, the difference was not statistically significant. Our results do not supportthe proposal that secondline chemotherapy could be effective in patients with MPM.     

Meta‐analysis of trials comparing toremifene with tamoxifen and factors predicting outcome of antiestrogen therapy in postmenopausal women with breast cancer

Metaanalysis of all clinical data was conducted to compare toremifene 40–60mg/day (TOR) with tamoxifen 20–40mg/day (TAM) in postmenopausal women with estrogen receptor (ER) positive or ER unknown advanced breast cancer and assess factors predicting treatment outcome. Data from five randomized parallel group studies (all studies) were combined. Efficacy variables were the response rate in all studies and also the time to treatment failure and survival in the three major studies (pivotal studies).Of the 1421 patients, 725 received TOR and 696 TAM. Response rates were 24.0 and 25.3, respectively (p=0.675) with 95 confidence interval (95 CI) for the difference –5.3 to 3.4. Of the 1157 patients in the pivotal studies, 75 had progressed and 50 expired. Median treatment times were 4.9 months in TOR and 5.3 months in TAM groups (p=0.762, hazard ratio 0.98 with 95 CI 0.87–1.11). Median survival times were 31.0 (TOR) and 33.1 (TAM) months (p=0.758, hazard ratio 0.98 with 95 CI 0.83–1.15). All results are consistent with the criteria of statistical equivalence between TOR and TAM. More patients in TAM (20) than in TOR (14, p=0.007) discontinued the treatment prematurely but overall the treatments were well tolerated. As the treatments were equally effective all data were analyzed together for predictive factors. High tumor ER concentration, long disease free time, soft tissue metastases, few metastatic sites, and good performance status all independently predicted longer survival (p<0.001). Previous adjuvant tamoxifen predicted shorter survival (p=0.008). Objective response to treatment or disease stabilization for at least 12 months both predicted prolonged survival (p=0.001).TOR 60mg/day and TAM are equally effective and well tolerated in the treatment of advanced breast cancer in postmenopausal women. Probability of survival may be predicted based on patient characteristics and on the initial response to the treatment.     

A retrospective study of high-dose toremifene treatment for patients with aromatase inhibitor refractory advanced or metastatic hormone receptor-positive breast cancer

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.