New developments in chemotherapy of advanced breast cancer
New developments in chemotherapy of advanced breast cancer
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DOI：
10.1023/a:1008318725670
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发表时间：
1999-01-01
影响因子：
50.5
通讯作者：
Canetta, R
中科院分区：
文献类型：
--
作者：
Lebwohl, DE;Canetta, R
蒽环类和紫杉烷类是治疗晚期乳腺癌最有效的两类化疗药物。最近的研究已经调查了包括多柔比星（Dox）和紫杉醇的组合疗法。在ECOG进行的一项III期研究中，比较了Dox/紫杉醇与Dox与紫杉醇，确定了该联合治疗的疗效。该组合在响应率和疾病进展时间方面上级Dox或紫杉醇，表明该组合为转移性乳腺癌的一线治疗提供了新的标准[1]。使用更高剂量的Dox和使用更短输注时间的紫杉醇的II期研究表明，可以进一步优化组合; Gianni报告使用Dox 60 mg/m2（2），然后在3小时内给予紫杉醇175 mg/m2（2），客观缓解率为94%[2]。更积极的方案与增强的心脏毒性有关;然而，通过限制阿霉素的暴露，可以避免这种毒性。新的治疗方案现已进入III期临床研究，今后治疗该病的进展将取决于新药物的引进。目前正在研究两种新药作为Dox和/或紫杉醇的增效剂的随机III期试验。一种是来自Genentech的针对HER-2/neu癌基因的单克隆抗体（赫赛汀，曲妥珠单抗），其在>25%的乳腺癌中过表达[3]。最近的结果表明，赫赛汀联合紫杉醇（或与Dox+环磷酰胺方案）诱导更高的反应率（RR），并缩短疾病进展时间，与单独化疗相比。第二种药物N，N-二乙基-2-[4-（苯甲基）-苯氧基]乙胺盐酸盐（DPPE，BMS-21738001）与Dox联合使用时，RR高于先前单独使用Dox时观察到的RR [4]。Dox与Dox + DPPE的随机试验正在进行中。化学增效的可能机制进行了讨论。随着新的蒽环类/紫杉烷组合在疾病的早期阶段确立，将出现对有效的、非交叉耐药的挽救治疗方案的需求。
Anthracyclines and taxanes are the two most active classes of chemotherapy for the treatment of advanced breast cancer. Recent studies have investigated combination therapy including doxorubicin (Dox) and paclitaxel. The efficacy of this combination has been established in a phase III study conducted by ECOG, comparing Dox/paclitaxel versus Dox versus paclitaxel. The combination is superior to Dox or paclitaxel with respect to response rate and time to disease progression, indicating that the combination provides a new standard for the first line treatment of metastatic breast cancer [Ij. Phase II studies using higher doses of Dox and using shorter infusions of paclitaxel have suggested the combination can be further optimised; Gianni reported a 94% objective response rate using Dox 60 mg/m(2) followed by paclitaxel 175 mg/m(2) given over three hours [2]. The more active regimens are associated with enhanced cardiotoxicity; this toxicity can be avoided, however, by limiting the exposure to doxorubicin. The newer regimens have now been moved into phase III studies.Future progress for this disease will depend on the introduction of new agents. Two novel drugs are currently being investigated in randomised phase III trials as potentiators of Dox and/or paclitaxel. One is a monoclonal antibody from Genentech (Herceptin, trastuzumab) directed at the HER-2/neu oncogene, which is overexpressed in >25% of breast cancers [3]. Recent results indicate that Herceptin in combination with paclitaxel (or with a Dox plus cyclophosphamide regimen) induces a higher response rate (RR) and prolongs the time to disease progression when compared to chemotherapy alone. The second agent N,N-diethyl-2[4- (phenylmethyl)-phenoxy] ethanamine.HCl (DPPE, BMS-21738001), when combined with Dox, was associated with a higher RR than previously observed with Dox alone [4]. A randomised trial of Dox versus Dox plus DPPE is ongoing. The possible mechanisms underlying chemo-potentiation by these agents are discussed. As new anthracycline/taxane combinations establish themselves in earlier stages of the disease, the need for effective, non-cross resistant salvage regimens will emerge.