Luck H J, Thomssen C, duBois A, Lisboa B W, Untch M, Kuhnle H, Konecny G, Janicke F, Meerpohl H G, Lindner C, Hecker D, Diergarten K
Department of Obstetrics and Gynecoloy, Frauenklinik der Medizinischen Hochschule, Hannover, Germany.
Semin Oncol. 1996 Feb;23(1 Suppl 1):33-6.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), the first taxane to be used routinely in clinical practice, has aroused considerable interest for its high single-agent activity in breast cancer and its novel mechanism of action. The 4' epimer of doxorubicin, epirubicin is an agent with high activity against breast cancer but a lower rate of toxic side effects, especially cardiotoxic events, than its parent compound. Although the paclitaxel/doxorubicin combination has yielded response rates between 63% and 94% in phase I/II studies, some severe cardiotoxic events were reported. The rationale for our study was to evaluate the paclitaxel/epirubicin combination, focusing mainly on cardiotoxicity. In all, 57 patients with metastatic breast cancer entered the study, 28% of whom had primary metastatic breast cancer with large tumors at the primary site. Half of the patients had received adjuvant chemotherapy. Study medication consisted of 60 mg/m2 epirubicin given intravenously over 1 hour, followed by paclitaxel 175 mg/m2 administered as a 3-hour intravenous infusion after premedication with steroids, antihistamines, and H2 antagonists. The main toxicity was neutropenia (World Health Organization toxicity index grade 3/4, 72%). Other hematologic side effects were rare and no febrile neutropenia was reported. Peripheral neuropathy, arthralgia, and myalgia were mild (only World Health Organization grade 1 and 2). All patients had alopecia. The paclitaxel dose was escalated to 200 mg/m2 in eight patients, four of whom received a further escalation to 225 mg/m2. Severe neutropenia necessitated dose reductions in eight patients. No cardiac adverse events were reported. Of 41 patients evaluable for response, seven had complete remissions and 21 had partial remissions (68%). An additional 12 patients (29%) had stable disease. The combination of paclitaxel 175 mg/m2 and epirubicin 60 mg/m2 can be administered safely to patients with metastatic breast cancer. Although response was not the primary end point of this trial, the response data are nonetheless encouraging and suggest that further evaluation of the role of this combination in the first-line treatment of metastatic breast cancer is warranted.
紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）是首个在临床实践中常规使用的紫杉烷类药物，因其在乳腺癌中具有较高的单药活性及其新颖的作用机制而引起了广泛关注。表柔比星是阿霉素的4'差向异构体，是一种对乳腺癌具有高活性但毒性副作用发生率低于其母体化合物的药物，尤其是心脏毒性事件。尽管在I/II期研究中，紫杉醇/阿霉素联合用药的缓解率在63%至94%之间，但仍有一些严重心脏毒性事件的报道。我们开展这项研究的目的是评估紫杉醇/表柔比星联合用药，主要关注心脏毒性。共有57例转移性乳腺癌患者进入该研究，其中28%的患者为原发性转移性乳腺癌，原发部位有大肿瘤。一半的患者接受过辅助化疗。研究用药包括静脉滴注1小时给予表柔比星60mg/m²，随后在使用类固醇、抗组胺药和H2拮抗剂进行预处理后，静脉滴注3小时给予紫杉醇175mg/m²。主要毒性为中性粒细胞减少（世界卫生组织毒性指数3/4级，72%）。其他血液学副作用罕见，未报告发热性中性粒细胞减少。周围神经病变、关节痛和肌痛较轻（仅世界卫生组织1级和2级）。所有患者均有脱发。8例患者的紫杉醇剂量增至200mg/m²，其中4例进一步增至225mg/m²。8例患者因严重中性粒细胞减少需要降低剂量。未报告心脏不良事件。在41例可评估缓解情况的患者中，7例完全缓解，21例部分缓解（68%）。另外12例患者（29%）病情稳定。对于转移性乳腺癌患者，可安全给予175mg/m²紫杉醇和60mg/m²表柔比星联合用药。尽管缓解情况并非该试验的主要终点，但缓解数据仍然令人鼓舞，表明有必要进一步评估该联合用药在转移性乳腺癌一线治疗中的作用。
