Köhler U, Olbricht S S, Fuechsel G, Kettner E, Richter B, Ridwelski K
Department of Obstetrics and Gynecology, University of Leipzig, Germany.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-40-S17-43.
Phase I/II trials have shown that combination of an anthracycline with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) represents a high-potency therapy for treatment of patients with metastatic breast cancer, with response rates exceeding 90%. This phase II trial was conducted to test the tolerability and efficacy of weekly epirubicin plus paclitaxel as second-line therapy for patients with pretreated metastatic breast cancer. In this study, 35 patients with previous hormone therapy and/or chemotherapy were treated at a weekly dose of paclitaxel 80 mg/m2 with epirubicin 35 mg/m2 (10 patients, 123 cycles) or paclitaxel 80 mg/m2 with epirubicin 25 mg/m2 (25 patients, 218 cycles). The dose reduction of anthracyclines became necessary due to severe hemotoxicity (neutropenia World Health Organization grade 3 to 4 in 30.2% of cycles). The therapy schema included a 2-week therapy interval after each treatment period of 6 weeks, with treatment continued until response or disease progression. Overall, 18 patents (51.4%) presented with responses (complete response or partial response) to therapy, with seven (20%) achieving a complete response after six to 18 cycles. In three cases (8.6%), tumor state was unchanged for a median interval of 11 weeks (range, 5 to 20 weeks). Progressive disease was observed in seven cases (20%), and seven patients (20%) were not evaluable. Following epirubicin dose reduction, neutropenia World Health Organization grade 3 to 4 occurred in only 18.1% of cycles. Referring to nonhematologic toxicity, alopecia exceeded World Health Organization grade 2. Other nonhematologic toxicities exceeding grade 2 were observed in only a few courses and were not statistically relevant. No clinically relevant deterioration of cardiac function was observed at a median cumulative dose of epirubicin 285 mg/m2 (maximum cumulative dose, 630 mg/m2). This study has substantiated that the schedule used is highly efficient and well tolerated as second-line chemotherapy for patients with metastatic breast cancer.
I/II期试验表明，蒽环类药物与紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）联合使用是治疗转移性乳腺癌患者的一种高效疗法，有效率超过90%。本II期试验旨在测试每周使用表柔比星加紫杉醇作为一线转移性乳腺癌患者二线治疗的耐受性和疗效。在本研究中，35例先前接受过激素治疗和/或化疗的患者接受治疗，紫杉醇剂量为80mg/m²，表柔比星剂量为35mg/m²（10例患者，123个周期）或紫杉醇80mg/m²，表柔比星25mg/m²（25例患者，218个周期）。由于严重的血液毒性（30.2%的周期出现世界卫生组织3至4级中性粒细胞减少），有必要减少蒽环类药物的剂量。治疗方案包括每6周治疗期后有2周的治疗间隔，治疗持续至出现反应或疾病进展。总体而言，18例患者（51.4%）对治疗有反应（完全缓解或部分缓解），7例（20%）在6至18个周期后实现完全缓解。3例患者（8.6%）肿瘤状态无变化，中位间隔时间为11周（范围为5至20周）。7例患者（20%）出现疾病进展，7例患者（20%）无法评估。表柔比星剂量减少后，世界卫生组织3至4级中性粒细胞减少仅出现在18.1%的周期中。关于非血液学毒性，脱发超过世界卫生组织2级。其他超过2级的非血液学毒性仅在少数疗程中观察到，且无统计学意义。在表柔比星中位累积剂量为285mg/m²（最大累积剂量为630mg/m²）时，未观察到临床相关的心脏功能恶化。本研究证实，所采用的方案作为转移性乳腺癌患者的二线化疗具有高效性和良好的耐受性。
