Doxorubicin/taxane combinations: cardiac toxicity and pharmacokinetics.
Doxorubicin/taxane combinations: cardiac toxicity and pharmacokinetics.
复制标题
阿霉素/紫杉烷组合：心脏毒性和药代动力学。
作者：
J. Sparano
阿霉素和紫杉醇、紫杉醇和多西紫杉醇（taxoere; Rhône-Poulenc Rorer, Collegeville， PA）是治疗转移性乳腺癌最有效的细胞毒性药物。鉴于它们的活性、相对非交叉耐药、部分非重叠毒性和不同的作用机制，有一个明确的理由将这些药物联合用于晚期和早期疾病。阿霉素/紫杉醇和阿霉素/多西紫杉醇的I期和II期试验均有报道。两种组合的反应率普遍较高。一些研究小组报告，如果阿霉素累积剂量超过360mg /m2，用阿霉素/紫杉醇治疗的患者发生充血性心力衰竭的风险高得令人无法接受。阿霉素/多西他赛联合用药未观察到类似的效果。这可能是由紫杉醇消除阿霉素的药代动力学干扰所解释的，这种影响高度依赖于给药间隔和紫杉醇药物输注持续时间。阿霉素/多西他赛没有观察到这种相互作用，这为含多西他赛的组合没有增强心脏毒性提供了解释。比较阿霉素/紫杉烷联合治疗与标准方案的III期试验已经完成并正在进行中，这将有助于确定在早期和晚期疾病中，联合使用这些药物是否比顺序使用这些药物更有优势。
Doxorubicin and the taxanes, paclitaxel and docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA), are among the most active cytotoxic agents for the treatment of metastatic breast cancer. Given their activity, relative non-cross-resistance, partially non-overlapping toxicities, and differing mechanisms of action, there is a clear rationale for combining these agents for both advanced and early stage disease. Phase I and II trials have been reported for both doxorubicin/paclitaxel and doxorubicin/docetaxel. Response rates have been generally high for both combinations. Some groups have reported an unacceptably high risk of congestive heart failure in patients treated with some schedules of doxorubicin/paclitaxel if the cumulative doxorubicin dose exceeded 360 mg/m2. A similar effect has not been observed with doxorubicin/docetaxel combinations. This is likely explained by a pharmacokinetic interference of doxorubicin elimination by paclitaxel, an effect that is highly dependent on the interval between administration of the drugs and the duration of the paclitaxel drug infusion. Such an interaction has not been observed with doxorubicin/docetaxel, providing an explanation for the lack of enhanced cardiotoxicity with docetaxel-containing combination. Phase III trials comparing doxorubicin/taxane combinations with standard regimens have been completed and are in progress, and should help define whether the use of these drugs in combination offers any advantage over their use in a sequential fashion in both early and advanced disease.