Palmeri S, Leonardi V, Tamburo De Bella M, Morabito A, Vaglica M, Accurso V, Ferraù F, Failla G, Agostara B, Massidda B, Valenza R, Fanelli M, Gasparini G
Istituto di Clinica Medica, Cattedra di Oncologia Medica, Università di Palermo, Italy.
Oncology. 2002;63(3):205-12. doi: 10.1159/000065466.
We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer.
A total of 73 patients with PS (ECOG) 0-2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m2 by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m2, by i.v. 60 min infusion. Cycles were repeated every 28 days.
Overall, the median number of administered cycles was 6 (range 1-14). The most common toxicity was hematological, with 56.2% of the patients who experienced grade 3-4 neutropenia. However, febrile neutropenia occurred only in 2.8% of the cases. The median cumulative dose of doxorubicin was 350 mg/m2 (range 50-700 mg/m2). Eleven patients (15.4%) were documented to have >10% but <20% decrease in the left ventricular ejection fraction. No case of congestive heart failure was recorded. No patient experienced treatment-related death. Among the 68 evaluable patients, the overall objective response rate was 73.5% (95% confidence limits: 63-84%): 10 patients (14.7%) obtained a complete remission and 40 (58.8%) had a partial response. Only 10 patients (14.7%) experienced progressive disease. The median duration of response was 10 months (2-54+).
This sequential treatment with doxorubicin and docetaxel is an effective, feasible and a well-tolerated regimen. The main toxicity was neutropenia. The lack of cardiotoxicity is an important advantage of such a doxorubicin-docetaxel combination and it justifies phase III comparative studies with other anthracyclines/taxanes containing schedules in both advanced and early-stage breast cancer.
我们开展了一项多机构II期研究,以评估阿霉素和多西他赛序贯治疗方案对初治晚期乳腺癌女性患者的耐受性和活性。
共有73例PS(ECOG)0 - 2、年龄<70岁且骨髓、肾、肝和心脏功能良好的患者纳入研究(13例III B期和60例IV期)。给药方案为第1天静脉注射阿霉素50mg/m²,30分钟推注,次日静脉输注多西他赛75mg/m²,60分钟滴注。每28天重复一个周期。
总体而言,给药周期的中位数为6个(范围1 - 14个)。最常见的毒性是血液学毒性,56.2%的患者出现3 - 4级中性粒细胞减少。然而,发热性中性粒细胞减少仅发生在2.8%的病例中。阿霉素的累积剂量中位数为350mg/m²(范围50 - 700mg/m²)。11例患者(15.4%)记录显示左心室射血分数下降>10%但<20%。未记录到充血性心力衰竭病例。无患者发生与治疗相关的死亡。在68例可评估患者中,总体客观缓解率为73.5%(95%置信区间:63 - 84%):10例患者(14.7%)获得完全缓解,40例(58.8%)部分缓解。仅10例患者(14.7%)疾病进展。缓解持续时间中位数为10个月(2 - 54 +)。
阿霉素和多西他赛的这种序贯治疗是一种有效、可行且耐受性良好的方案。主要毒性是中性粒细胞减少。缺乏心脏毒性是这种阿霉素 - 多西他赛联合方案的一个重要优势,这为在晚期和早期乳腺癌中与其他含蒽环类/紫杉类方案进行III期对比研究提供了依据。