Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.
Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials.
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DOI：
10.1016/s0140-6736(11)61625-5
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发表时间：
2012-02-04
期刊：
影响因子：
168.9
通讯作者：
Wood, W.
中科院分区：
文献类型：
--
作者：
Albain, K.;Anderson, S.;Arriagada, R.;Barlow, W.;Bergh, J.;Bliss, J.;Buyse, M.;Cameron, D.;Carrasco, E.;Clarke, M.;Correa, C.;Coates, A.;Collins, R.;Costantino, J.;Cutter, D.;Cuzick, J.;Darby, S.;Davidson, N.;Davies, C.;Davies, K.;Delmestri, A.;Di Leo, A.;Dowsett, M.;Elphinstone, P.;Evans, V.;Ewertz, M.;Gelber, R.;Gettins, L.;Geyer, C.;Goldhirsch, A.;Godwin, J.;Gray, R.;Gregory, C.;Hayes, D.;Hill, C.;Ingle, J.;Jakesz, R.;James, S.;Kaufmann, M.;Kerr, A.;MacKinnon, E.;McGale, P.;McHugh, T.;Norton, L.;Ohashi, Y.;Paik, S.;Pan, H. C.;Perez, E.;Peto, R.;Piccart, M.;Pierce, L.;Pritchard, K.;Pruneri, G.;Raina, V.;Ravdin, P.;Robertson, J.;Rutgers, E.;Shao, Y. F.;Swain, S.;Taylor, C.;Valagussa, P.;Viale, G.;Whelan, T.;Winer, E.;Wang, Y.;Wood, W.
乳腺癌辅助化疗方案之间的疗效存在中度差异是合理的，并可能影响治疗选择。我们寻求任何这样的差异。我们对随机试验进行了个体患者数据荟萃分析，比较：任何紫杉烷加蒽环类药物方案与相同或多种非紫杉烷化疗方案（n=44 000）;一种蒽环类药物方案与另一种方案（n=7000）或与环磷酰胺、甲氨蝶呤和氟尿嘧啶（CMF; n=18 000）;以及多药化疗与无化疗（n=32 000）。 这三种药物以及蒽环类药物阿霉素（A）和表阿霉素（E）的预定剂量用于定义标准CMF、标准4AC、CAF和CEF。报告了对数秩乳腺癌死亡率比（RR）。在以蒽环类为基础的固定对照方案中增加4个单独的紫杉烷周期的试验中，延长治疗时间，乳腺癌死亡率降低（RR 0.86，SE 0.04，双侧显著性[2 p]= 0.0005）。在四个这样的额外紫杉烷周期的试验中，通过额外的其他细胞毒性药物周期来抵消对照组中的紫杉烷，大约是非紫杉烷剂量的两倍，没有显著差异（RR 0.94，SE 0.06，2 p = 0.33）。CMF治疗对照的试验显示，标准4AC和标准CMF相当（RR 0·98，SE 0·05，2 p =0·67），但累积剂量显著高于标准4AC（例如CAF或CEF）的基于蒽环类药物的方案上级优于标准CMF（RR 0·78，SE 0·06，2 p =0·0004）。与未化疗相比的试验也表明，CAF（RR 0.64，SE 0.09，2 p <0.0001）比标准4AC（RR 0.78，SE 0.09，2 p = 0.01）或标准CMF（RR 0.76，SE 0.05，2 p <0.0001）的死亡率降低更大。在所有涉及基于紫杉烷或蒽环类药物治疗方案的荟萃分析中，比例风险降低几乎不受年龄、淋巴结状态、肿瘤直径或分化（中度或较差;少数分化良好）、雌激素受体状态或他莫昔芬使用的影响。因此，在很大程度上独立于年龄（至少70岁）或肿瘤特征，我们目前选择的患者在这些试验中，一些紫杉烷加蒽环类或更高的累积剂量蒽环类方案（不需要干细胞）减少乳腺癌死亡率，平均约三分之一。10-年总死亡率差异超过乳腺癌死亡率差异，尽管紫杉烷，蒽环类药物和其他毒性。10-乳腺癌死亡率降低三分之一的年收益取决于没有化疗的绝对风险（对于雌激素受体阳性疾病，这是适当内分泌治疗的风险）。低绝对风险意味着低绝对获益，但缺乏有关肿瘤基因表达标志物或定量免疫组化的信息，这些信息可能有助于预测风险、化疗敏感性或两者兼而有之。英国癌症研究;英国心脏基金会;英国医学研究理事会。
Moderate differences in efficacy between adjuvant chemotherapy regimens for breast cancer are plausible, and could affect treatment choices. We sought any such differences. We undertook individual-patient-data meta-analyses of the randomised trials comparing: any taxane-plus-anthracycline-based regimen versus the same, or more, non-taxane chemotherapy (n=44 000); one anthracycline-based regimen versus another (n=7000) or versus cyclophosphamide, methotrexate, and fluorouracil (CMF; n=18 000); and polychemotherapy versus no chemotherapy (n=32 000). The scheduled dosages of these three drugs and of the anthracyclines doxorubicin (A) and epirubicin (E) were used to define standard CMF, standard 4AC, and CAF and CEF. Log-rank breast cancer mortality rate ratios (RRs) are reported. In trials adding four separate cycles of a taxane to a fixed anthracycline-based control regimen, extending treatment duration, breast cancer mortality was reduced (RR 0·86, SE 0·04, two-sided significance [2p]=0·0005). In trials with four such extra cycles of a taxane counterbalanced in controls by extra cycles of other cytotoxic drugs, roughly doubling non-taxane dosage, there was no significant difference (RR 0·94, SE 0·06, 2p=0·33). Trials with CMF-treated controls showed that standard 4AC and standard CMF were equivalent (RR 0·98, SE 0·05, 2p=0·67), but that anthracycline-based regimens with substantially higher cumulative dosage than standard 4AC (eg, CAF or CEF) were superior to standard CMF (RR 0·78, SE 0·06, 2p=0·0004). Trials versus no chemotherapy also suggested greater mortality reductions with CAF (RR 0·64, SE 0·09, 2p<0·0001) than with standard 4AC (RR 0·78, SE 0·09, 2p=0·01) or standard CMF (RR 0·76, SE 0·05, 2p<0·0001). In all meta-analyses involving taxane-based or anthracycline-based regimens, proportional risk reductions were little affected by age, nodal status, tumour diameter or differentiation (moderate or poor; few were well differentiated), oestrogen receptor status, or tamoxifen use. Hence, largely independently of age (up to at least 70 years) or the tumour characteristics currently available to us for the patients selected to be in these trials, some taxane-plus-anthracycline-based or higher-cumulative-dosage anthracycline-based regimens (not requiring stem cells) reduced breast cancer mortality by, on average, about one-third. 10-year overall mortality differences paralleled breast cancer mortality differences, despite taxane, anthracycline, and other toxicities. 10-year gains from a one-third breast cancer mortality reduction depend on absolute risks without chemotherapy (which, for oestrogen-receptor-positive disease, are the risks remaining with appropriate endocrine therapy). Low absolute risk implies low absolute benefit, but information was lacking about tumour gene expression markers or quantitative immunohistochemistry that might help to predict risk, chemosensitivity, or both. Cancer Research UK; British Heart Foundation; UK Medical Research Council.