Vici P, Capomolla E, Foggi P, Carpano S, Conti F, Paoletti G, Cauchi C, Giacinti L, Leonetti C, Giannarelli D, Lopez M
Division of Medical Oncology B, Regina Elena Institute for Cancer Research, Rome, Italy.
J Exp Clin Cancer Res. 2006 Mar;25(1):39-44.
The treatment of refractory metastatic breast cancer is primarily palliative, without a significant impact on overall survival. Among the innovative combinations in this unfavourable setting, paclitaxel and gemcitabine showed a possible synergistic action and an encouraging activity in some clinical trials. This phase II study was carried out to evaluate paclitaxel-gemcitabine combination in very heavily pretreated advanced breast cancer on a bi-weekly schedule.Thirty-nine women with advanced breast cancer were treated with paclitaxel 150 mg/m2 as 3 hrs infusion, and gemcitabine 1,500 mg/m2 as 30 mins infusion, both drugs administered on days 1, 15, with cycles repeated every 28 days. All but two patients received granulocyte colony stimulating factor (G-CSF) on days 7 to 9 and 20 to 22 of every cycle. More than two third (71%) of the patients had previously received two or more chemotherapy regimens for advanced disease, including almost all active agents in this disease. Objective responses were observed in 18 out of 34 evaluable patients (53%; 95% CI, 36% to 70%). Disease remained stable in 7 patients (21%). Responses by sites were 67% in soft tissue and in bone, and 48% in visceral disease. Median time to progression and overall survival were 9 and 20 months, respectively. Treatment was well tolerated, with G3-4 neutropenia in 8%, and G 1-2 thrombocytopenia in 13% of the patients; non-hematological toxicities were mild, with G3 hepatotoxicity in 5% of the patients, and G3 peripheral neurotoxicity in 10% of the patients. Biweekly paclitaxel/gemcitabine combination with G-CSF support appears to be very active as salvage therapy in heavily pretreated breast cancer patients, with a very favourable safety profile.
难治性转移性乳腺癌的治疗主要是姑息性的，对总生存期没有显著影响。在这种不利情况下的创新联合治疗方案中，紫杉醇和吉西他滨在一些临床试验中显示出可能的协同作用和令人鼓舞的活性。这项II期研究旨在评估紫杉醇-吉西他滨联合方案在接受过大量预处理的晚期乳腺癌患者中按每两周一次的给药方案的疗效。39例晚期乳腺癌女性患者接受紫杉醇150mg/m²，静脉输注3小时，吉西他滨1500mg/m²，静脉输注30分钟，两种药物均在第1天和第15天给药，每28天重复一个周期。除两名患者外，所有患者在每个周期的第7至9天和第20至22天接受粒细胞集落刺激因子（G-CSF）治疗。超过三分之二（71%）的患者此前因晚期疾病接受过两种或更多化疗方案，包括该疾病几乎所有的活性药物。34例可评估患者中有18例观察到客观缓解（53%；95%CI，36%至70%）。7例患者（21%）疾病稳定。软组织和骨转移灶的缓解率为67%，内脏转移灶的缓解率为48%。中位疾病进展时间和总生存期分别为9个月和20个月。治疗耐受性良好，8%的患者出现3-4级中性粒细胞减少，13%的患者出现1-2级血小板减少；非血液学毒性较轻，5%的患者出现3级肝毒性，10%的患者出现3级周围神经毒性。每两周一次的紫杉醇/吉西他滨联合方案加用G-CSF支持作为挽救治疗在接受过大量预处理的乳腺癌患者中似乎非常有效，且安全性非常好。
