Nabholtz J M, Smylie M, Mackey J R, Noel D, Paterson A H, al-Tweigeri T, Au D, Sansregret E, Delorme F, Riva A
Cross Cancer Institute Edmonton, Alberta, Canada.
Oncology (Williston Park). 1997 Aug;11(8 Suppl 8):37-41.
Preliminary results from phase I trials suggest that the use of docetaxel (Taxotere) and doxorubicin (Adriamycin) is a well tolerated and highly active combination regimen for patients with metastatic breast cancer. The maximum tolerated dose of this combination was 50 mg/m2 of doxorubicin given as an intravenous bolus followed 1 hour later with 75 mg/m2 of docetaxel given as a 1-hour intravenous infusion. Because cardiotoxicity was not observed with this combination, we added cyclophosphamide (Cytoxan, Neosar) in a phase II trial to determine the antitumor activity and tolerability of this 3-drug combination as first-line therapy in patients with metastatic breast cancer. Preliminary results from this study indicate that the Taxotere/ Adriamycin/Cyclophosphamide (TAC) combination produces response rates of up to 80%. However, frequent grade 4 neutropenia was seen in 68% of cycles, febrile neutropenia in 5.5% of cycles, and grade 3 to 4 infection in .8% of cycles. Cardiac toxicity was rare, with 1 case of reversible congestive heart failure (2%), which occurred 2 months after completion of chemotherapy. These preliminary data show that TAC is highly active and that docetaxel did not significantly increase the cardiotoxicity of doxorubicin. Phase III studies in both the first-line and adjuvant settings are warranted.
I期试验的初步结果表明，对于转移性乳腺癌患者，多西他赛（泰索帝）和阿霉素（阿霉素）联合使用耐受性良好且活性高。该联合方案的最大耐受剂量为静脉推注阿霉素50mg/m²，1小时后静脉输注多西他赛75mg/m²，持续1小时。由于该联合方案未观察到心脏毒性，我们在II期试验中加入环磷酰胺（环磷酰胺，新磷酰胺），以确定这种三联药物组合作为转移性乳腺癌患者一线治疗的抗肿瘤活性和耐受性。这项研究的初步结果表明，泰索帝/阿霉素/环磷酰胺（TAC）联合方案的有效率高达80%。然而，68%的疗程出现频繁的4级中性粒细胞减少，5.5%的疗程出现发热性中性粒细胞减少，0.8%的疗程出现3至4级感染。心脏毒性罕见，有1例可逆性充血性心力衰竭（2%），发生在化疗结束后2个月。这些初步数据表明，TAC活性高，多西他赛并未显著增加阿霉素的心脏毒性。有必要在一线和辅助治疗环境中进行III期研究。
