【摘要】 目的化疗仍是晚期乳腺癌治疗的基石,如何选择有效化疗方案及药物值得进一步的临床研究。本研究探讨含铂方案治疗晚期乳腺癌的疗效和安全性,对比分析不同治疗线数及不同分子分型晚期乳腺癌对以铂类药物为基础的方案治疗疗效的差异。方法回顾性分析江苏省肿瘤医院2010-01-01-2015-05-31以铂类药物为基础的方案治疗238例晚期乳腺癌患者的临床资料。一线化疗124例,二线61例,≥三线53例。铂类药物包括顺铂93例,给药方法为75mg/m²,一次性给药或分3d给药;卡铂33例,按血液浓度-时间曲线下面积取5计算,一次性给药;洛铂112例,30mg/m²,一次性给药。联合药物包括吉西他滨（1 000mg/m²,d₁、d₈）、长春瑞滨（25mg/m²,d₁、d₈）、紫杉醇或紫杉醇脂质体（175mg/m²,d₁）和多西紫杉醇（75mg/m²,d₁）,21²8d为1个周期。至少化疗2个周期后评估疗效及毒副作用。结果入组238例患者均可评价疗效,其中完全缓解（complete remission,CR）2例（0.8%）,部分缓解（partial remission,PR）57例（23.9%）,疾病稳定（stable disease,SD）134例（56.3%）,疾病进展（progressive disease,PD）45例（18.9%）,疾病控制率（disease control rate,DCR）为81.1%。全组患者中位疾病进展时间（time to progression,TTP）为6.0个月（95%CI为5.4⁶.6个月）。亚组分析结果显示,一线化疗DCR为88.7%,二线为77.0%,三线为67.9%,3组比较差异有统计学意义,P=0.028。不同治疗线数TTP之间比较,差异有统计学意义,P<0.001。激素受体（hormone receptor,HR）状态亚组分析结果显示,HR阳性和阴性组DCR分别为79.9%和83.1%,两组比较差异无统计学意义,P=0.532。根据人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）状态分组,阴性和阳性组DCR分别为80.0%和84.1%,两组比较差异无统计学意义,P=0.608;中位TTP分别为6.0和7.0个月,两组比较差异有统计学意义,P=0.004。根据三阴性与非三阴性乳腺癌亚组分析,两组DCR分别为78.7%和81.9%,差异无统计学意义,P=0.795;中位TTP分别5.5和6.0个月,差异有统计学意义,P=0.014。3种铂类药物分层分析,顺铂、卡铂和洛铂DCR分别为89.2%、75.8%和75.9%,组间比较差异有统计学意义,P=0.042;而3种铂类药物治疗患者的中位TTP比较,差异无统计学意义,P=0.892。全组主要不良反应为血液学毒性、消化道反应及肝损伤,经对症处理后均好转,无治疗相关性死亡。结论含铂方案在晚期乳腺癌的治疗中具有较好的疗效,且毒副作用大部分可耐受;不同分子分型间DCR未发现差异,HER2阳性及非三阴性乳腺癌患者中位TTP更长;随着治疗线数增加,疗效下降,中位TTP缩短;3种铂类药物对比,含顺铂方案组显示出更优的疗效。更多还原

【Abstract】 OBJECTIVE Chemotherapy remains the cornerstone of treatment of advanced breast cancer.How to choose effective regimens and drugs is worthy of further clinical studies.Our studies is to evaluate the efficacy and toxicity of platinum-based chemotherapy in patients with advanced metastatic breast cancer and to compare the differences of efficacy in the first-line,second-line,multi-line treatments and different molecular subtypes.METHODS Totally 238 patients with advanced metastatic breast cancer infused with platinum-based regimen were analyzed retrospectively,124 were in the first-line treatment group,61 were in the second-line and 53 were in the third-line.The platinum drugs include three types,93 in cisplatin group(75mg/m~2,oncetime administration or divided into three days),33 in Carboplatin group(AUC=5,oncetime administration)and 112 in Lobaplatin group(30mg/m~2,oncetime administration).Combination therapy was given as follows:gemcitabine(1 000 mg/m~2)or vinorelbine(25 mg/m~2)on day 1,day 8;taxol(175mg/m~2),taxol liposomes(175mg/m~2)or docetaxel(75mg/m~2)on day 1.Twenty-one to twenty-eight days was a cycle.The efficacy and side effects were evaluated after at least two cycles of chemotherapy.RESULTS The efficacy could be evaluated in all patients with 2cases of CR(0.8%),57 cases of PR(23.9%),134 cases of SD(56.3%)and45cases of PD(18.9%).The disease control rate(DCR)was 81.1% and the median time to progression(TTP)of all patients was 6.0months(95%CI:5.4-6.6months).Subgroup analyzes:the DCR of first,second and third-line treatment was 88.7%,77.0% and 67.9%,the differences were significant(P=0.028).Also there were significant differences of mTTPs among the three groups(P<0.001).In stratified analysis by ER,PR and HER2 status,no significant differences were found between the DCR.There were significant differences(P=0.004)of mTTPs between HER2positive(6.0month)and negative groups(7.0 month),and also between the triple negative or non-triple negative groups(5.5 vs 6.0 month,P=0.014)except the steroid receptor positive and the negative groups.Stratified analysis by the platinum drugs,the DCR of cisplatin,Carboplatin and Lobaplatin groups were 89.2%,75.8% and 75.9%,the differences were significant(P=0.042),no significant differences were found among the three groups on mTTPs.The main side effects were myelosuppression,gastrointestinal reaction and liver dysfunction,without chemotherapy related death.CONCLUSIONS platinum-based chemotherapy for advanced metastatic breast cancer patients is effective and well tolerated.With the increment of chemotherapy lines,the lower effective rate and more adverse reactions can be found.In different molecular subtypes of breast cancer,there were no differences between the DCR.The mTTP of HER2 positive patients were longer than that of HER2 negative ones,and with the same result between non-triple-negative and triple-negative groups;cisplatin based regimens showed better efficacy than the other two platinum-based regimens groups.更多还原