Cocconi G, Mambrini A, Quarta M, Vasini G, Bella M A, Ferrozzi F, Beretta M D
Medical Oncology Division, University Hospital, Parma, Italy.
Cancer. 2000 Jun 15;88(12):2731-8. doi: 10.1002/1097-0142(20000615)88:12<2731::aid-cncr11>3.0.co;2-9.
Vinorelbine (VI) and paclitaxel (TA) are among the most active single agents in the treatment of patients with breast carcinoma, and both have microtubules as their cytotoxic target. This Phase I-II study combined these 2 agents and used a 96-hour intravenous (i.v.) infusion of paclitaxel to maximize their cytotoxic activities.
Patients with metastatic breast carcinoma who were previously treated with chemotherapy were administered increasing doses of a 96-hour paclitaxel i.v. infusion from Days 1 to 5, with a first fixed dose of vinorelbine (12.5 mg/m(2) on Days 1 and 5) every 3 weeks. The dose of paclitaxel was then decreased starting from the previously established tolerated dose, and a second fixed dose of vinorelbine (15 mg/m(2) on Days 1 and 5) was given. This identified 2 acceptable doses of paclitaxel (110 mg/m(2) with VI 12.5 mg/m(2) and 90 mg/m(2) with VI 15 mg/m(2)). The latter was used in the subsequent Phase II study.
For the 50 patients treated with any dose, the complete response (CR) and the CR plus partial response (PR) rates were, respectively, 14% and 48% (95% confidence interval [CI], 34-67%). When only the 27 patients treated with the Phase II dose were considered, the figures were, respectively, 11% and 52% (95% CI, 42-62%). The median time to progression was 26 weeks, and the median survival 51 weeks. The dose-limiting toxicity was febrile neutropenia.
At the dose schedule identified for the Phase II study, the VI-TA-96 combination has considerable antitumor activity; pharmacoeconomic interest (it requires about half the doses of the agents administered singly); no major toxicity, except G4 neutropenia; and no need for premedication. This combination may be recommended as one of the most effective therapeutic options for patients with metastatic breast carcinoma who were pretreated mainly with anthracycline-containing chemotherapy.
长春瑞滨（VI）和紫杉醇（TA）是治疗乳腺癌最有效的单一药物之一，二者均以微管作为细胞毒性靶点。这项I-II期研究将这两种药物联合使用，并采用96小时静脉输注紫杉醇以最大化其细胞毒性活性。
既往接受过化疗的转移性乳腺癌患者，在第1至5天接受递增剂量的96小时紫杉醇静脉输注，每3周给予首个固定剂量的长春瑞滨（第1天和第5天为12.5mg/m²）。然后从先前确定的耐受剂量开始降低紫杉醇剂量，并给予第二个固定剂量的长春瑞滨（第1天和第5天为15mg/m²）。由此确定了2个可接受的紫杉醇剂量（VI 12.5mg/m²时为110mg/m²和VI 15mg/m²时为90mg/m²）。后者用于后续的II期研究。
对于接受任何剂量治疗的50例患者，完全缓解（CR）率和CR加部分缓解（PR）率分别为14%和48%（95%置信区间[CI]，34-67%）。仅考虑接受II期剂量治疗的27例患者时，相应数字分别为11%和52%（95%CI，42-62%）。中位进展时间为26周，中位生存期为51周。剂量限制性毒性为发热性中性粒细胞减少。
在II期研究确定的剂量方案下，VI-TA-96联合方案具有相当大的抗肿瘤活性；具有药物经济学优势（所需药物剂量约为单药给药的一半）；除4级中性粒细胞减少外无重大毒性；且无需预处理。对于主要接受含蒽环类化疗预处理的转移性乳腺癌患者，该联合方案可作为最有效的治疗选择之一推荐使用。
