Ries F, Duhem C, Kleiber K, Dicato M
Department of Hematology-Oncology, Centre Hospitalier de Luxembourg.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-48-S17-51.
Anthracyclines and taxanes are the most potent cytotoxic agents available for treating breast cancer. With combined therapy (either epirubicin or doxorubicin with paclitaxel [Taxol; Bristol-Myers Squibb Company, Princeton, NJ]), response rates of 70% to 90% have been reported. To achieve a maximal dose intensity per week, we decided to combine epirubicin 100 mg/m2 with escalating doses of paclitaxel, at successive dose levels of 135, 150, 165, and 180 mg/m2 in a 2-week schedule, with administration of subcutaneous granulocyte colony-stimulating factor 5 microg/kg from days 2 through 10. To date, 16 patients have been included, with six patients treated at level 1 (100/135 mg/m2 epirubicin/paclitaxel), four at level 2 (100/150 mg/m2), four at level 3 (100/165 mg/m2), and two at level 4 (100/180 mg/m2). The median age of all subjects is 55 years (range, 41 to 65 years). Five patients had received chemotherapy in the adjuvant setting. Of 79 treatment courses, 78 are evaluable for toxicity. The mean number of courses per patient is six (range, two to six courses). At dose level 1, one episode of febrile neutropenia with grade 4 thrombocytopenia occurred. No grade 4 extrahematologic adverse event has been noted so far. At dose level 2, we achieved a dose intensity per week of epirubicin 50 mg/m2 and paclitaxel 75 mg/m2, as expected. At dose level 3, the dose intensity per week was 47.5 mg/m2 and 78.8 mg/m2, respectively (expected 50 and 82.5 mg/m2). The current response rate, evaluated in 14 of 16 patients, is four complete remissions and eight partial remissions, for an overall response rate of 85%. Two patients had stable disease. Granulocyte colony-stimulating factor following epirubicin/paclitaxel on a 2-week schedule permits a very high dose intensity per week for both drugs and produces a high response rate in patients with advanced or metastatic breast cancer.
蒽环类药物和紫杉烷类药物是治疗乳腺癌最有效的细胞毒性药物。采用联合治疗（表柔比星或多柔比星与紫杉醇联合使用[紫杉醇；百时美施贵宝公司，新泽西州普林斯顿]），据报道缓解率为70%至90%。为了实现每周最大剂量强度，我们决定将表柔比星100mg/m²与递增剂量的紫杉醇联合使用，在2周的疗程中依次采用135、150、165和180mg/m²的剂量水平，并从第2天至第10天给予皮下注射粒细胞集落刺激因子5μg/kg。迄今为止，已纳入16例患者，其中6例在1级（表柔比星/紫杉醇100/135mg/m²）接受治疗，4例在2级（100/150mg/m²），4例在3级（100/165mg/m²），2例在4级（100/180mg/m²）。所有受试者的中位年龄为55岁（范围41至65岁）。5例患者在辅助治疗中接受过化疗。在79个疗程中，78个可评估毒性。每位患者的平均疗程数为6个（范围2至6个疗程）。在1级剂量水平，发生了1次4级血小板减少伴发热性中性粒细胞减少。迄今为止，未观察到4级血液学外不良事件。在2级剂量水平，我们实现了每周表柔比星50mg/m²和紫杉醇75mg/m²的剂量强度，与预期一致。在3级剂量水平，每周剂量强度分别为47.5mg/m²和78.8mg/m²（预期为50和82.5mg/m²）。在16例患者中的14例中评估的当前缓解率为4例完全缓解和8例部分缓解，总缓解率为85%。2例患者病情稳定。表柔比星/紫杉醇在2周疗程后使用粒细胞集落刺激因子可使两种药物每周达到非常高的剂量强度，并在晚期或转移性乳腺癌患者中产生高缓解率。
