Hortobagyi G N, Holmes F A, Theriault R L, Rahman Z, Buzdar A U
The Department of Breast Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030-4009, USA.
Semin Oncol. 1997 Aug;24(4 Suppl 11):S11-13-S11-19.
The development of anthracycline/paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) combinations has gone through several phases or generations. The first dose escalation studies used prolonged infusions of doxorubicin (48 to 72 hours) and paclitaxel (24 hours). Myelosuppression, mucositis, and neutropenic fever were dose limiting, and a sequence-dependent interaction was noted. In a second phase, doxorubicin was administered by bolus, without changing the schedule of the taxane. More recently, bolus doxorubicin was combined with 3-hour paclitaxel infusions. Higher doses of both agents were administered in this latter schedule, with higher overall response rates reported. Excessive cardiac toxicity was reported with the initial trials that used this schedule. Confirmatory studies are under way pursuing several alternatives to reduce the risk of cardiac toxicity; these include limiting the cumulative dose of doxorubicin, inserting an interval between the administration of the two drugs, and adding a cardioprotective agent to the combination. The high degree of antitumor activity of this combination is quite encouraging, and additional evaluation of this regimen in controlled trials is warranted in metastatic and high-risk primary breast cancer.
蒽环类药物/紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合用药的发展经历了几个阶段或代次。最初的剂量递增研究采用阿霉素长时间输注（48至72小时）和紫杉醇（24小时）。骨髓抑制、粘膜炎和中性粒细胞减少性发热是剂量限制性毒性，并且观察到了一种顺序依赖性相互作用。在第二阶段，阿霉素采用推注给药，而紫杉烷的给药方案不变。最近，推注阿霉素与3小时的紫杉醇输注联合使用。在此后一种给药方案中两种药物均给予了更高剂量，报告的总体缓解率更高。使用该给药方案的初始试验报告了过度的心脏毒性。正在进行确证性研究以寻求几种降低心脏毒性风险的替代方法；这些方法包括限制阿霉素的累积剂量、在两种药物给药之间插入一个间隔期以及在联合用药中添加一种心脏保护剂。这种联合用药的高度抗肿瘤活性相当令人鼓舞，在转移性和高危原发性乳腺癌的对照试验中对该方案进行进一步评估是有必要的。
