Papadimitriou C A, Dimopoulos M A, Ampela C, Louvrou-Fertaki A, Anagnostopoulos A, Athanassiades P, Stamatelopoulos S, Keramopoulos A
Department of Clinical Therapeutics, Alexandra Hospital, Athens University School of Medicine, Athens, Greece.
Oncology. 1998 Nov-Dec;55(6):533-7. doi: 10.1159/000011908.
Although the combination of paclitaxel with doxorubicin has yielded high response rates in metastatic breast cancer, severe cardiotoxic events have been reported in several patients. The rationale for our study was to evaluate the activity of paclitaxel/doxorubicin combination in patients with this disease but to avoid excessive cardiotoxicity. Therefore, we administered 4 cycles of doxorubicin/paclitaxel followed by 6 cycles of standard cyclophosphamide, methotrexate and 5-fluorouracil (CMF) regimen. Study medication consisted of doxorubicin 60 mg/m2 as a 15-min intravenous infusion followed by paclitaxel 175 mg/m2 as a 3-hour infusion. CMF regimen consisted of cyclophosphamide 600 mg/m2 as 1-hour intravenous infusion followed by methotrexate 40 mg/m2 and 5-fluorouracil 600 mg/m2 bolus injection. The main toxicity of doxorubicin/paclitaxel treatment phase was neutropenia (WHO grade 3/4, 58%), but we observed only one cardiac adverse event. Toxicities of the CMF treatment phase were not significant. Of 24 patients evaluable for response, 2 (8%) had complete responses and 11 (46%) achieved partial response. Ten additional patients (42%) had stable disease. The median time to progression was 12 months and the median overall survival was 18.5 months. The sequential administration of doxorubicin and paclitaxel followed by CMF appeared active and well tolerated in patients with metastatic breast cancer.
尽管紫杉醇与阿霉素联合用药在转移性乳腺癌中取得了较高的缓解率，但已有数例患者报告出现严重的心脏毒性事件。我们开展这项研究的目的是评估紫杉醇/阿霉素联合用药对该病患者的疗效，同时避免过度的心脏毒性。因此，我们先给予4个周期的阿霉素/紫杉醇治疗，随后给予6个周期的标准环磷酰胺、甲氨蝶呤和5-氟尿嘧啶（CMF）方案。研究用药包括阿霉素60mg/m²，静脉输注15分钟，随后是紫杉醇175mg/m²，输注3小时。CMF方案包括环磷酰胺600mg/m²，静脉输注1小时，随后是甲氨蝶呤40mg/m²和5-氟尿嘧啶600mg/m²推注。阿霉素/紫杉醇治疗阶段的主要毒性是中性粒细胞减少（世界卫生组织3/4级，58%），但我们仅观察到1例心脏不良事件。CMF治疗阶段的毒性不显著。在可评估缓解情况的24例患者中，2例（8%）完全缓解，11例（46%）部分缓解。另外10例患者（42%）病情稳定。中位疾病进展时间为12个月，中位总生存期为18.5个月。阿霉素和紫杉醇序贯给药后再给予CMF方案，对转移性乳腺癌患者似乎有效且耐受性良好。
