Dieras V, Extra J M, Bellissant E, Espie M, Morvan F, Pierga J Y, Mignot L, Tresca P, Marty M
Department of Oncology, Hopital Saint Louis, Paris, France.
J Clin Oncol. 1996 Dec;14(12):3097-104. doi: 10.1200/JCO.1996.14.12.3097.
To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer.
As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks.
Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%.
This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.
评估氟尿嘧啶（5FU）与长春瑞滨联合作为晚期乳腺癌患者一线治疗方案的抗肿瘤疗效和安全性。
按照II期成组序贯设计的七个连续步骤的定义，63例患者接受5FU 750mg/m²/天，连续输注5天，长春瑞滨30mg/m²在第1天和第5天进行短程静脉输注，每3周一次。
63例患者中有41例达到客观缓解，这使我们能够终止研究，并以90%的检验效能拒绝缓解率低于50%的假设。缓解率的无偏估计为61.6%。缓解率在以下方面无显著差异：（1）既往辅助治疗类型（无，n = 23；无蒽环类药物，n = 6；有蒽环类药物，n = 34）；（2）转移病灶部位；（3）转移部位数量。中位疾病进展时间为8.4个月。中位缓解持续时间为12.3个月，从首次评估完全缓解（CR）起，CR的中位持续时间为7.3个月。中位总生存时间为23个月（CR患者为28.1个月）。主要毒性（3级和4级）为中性粒细胞减少（90%的患者）、感染（12.7%）、粘膜炎（37%）和便秘（9.5%）。然而，大多数患者可在门诊接受治疗，中位相对剂量强度为86%。
这项采用成组序贯设计的II期研究表明，5FU与长春瑞滨联合是治疗乳腺癌首次转移进展的一种有效且耐受性良好的方案。它为先前接受过蒽环类辅助化疗或无法使用蒽环类药物的患者提供了一种替代方案。
