Lortholary A, Delozier T, Monnier A, Bourgeois H, Bougnoux P, Tubiana-Mathieu N, Riffaud J Ch, Besson D, Lotz V, Gamelin E
Centre Paul Papin, Angers, France.
Br J Cancer. 2003 Jun 2;88(11):1669-74. doi: 10.1038/sj.bjc.6600989.
The purpose of the study was to determine the efficacy and safety of docetaxel plus continuous infusion of 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracyclines. A total of 41 patients with histologically proven metastatic breast cancer and performance status 0-2, who had received at least one anthracycline-containing regimen, received docetaxel 85 mg m(-2) followed by continuous infusion of 5-FU 750 mg m(-2) day(-1) for 5 days every 3 weeks for up to eight cycles. All patients received corticosteroid premedication, but there was no prophylactic colony-stimulating factor support. The most frequent metastatic sites were the liver (61%), bone (29%), and lung (29%). All 41 patients were assessable for toxicity and 30 were eligible and assessable for efficacy. The objective response rate was 70.0% (95% CI: 53.6-86.4%) for the per protocol group and 53.7% (95% CI: 38.4-68.9%) for the intent-to-treat (ITT) population. For the ITT population, median duration of response was 8.4 months (95% CI: 6.7-12.2 months), median time to progression was 6.7 months (95% CI 5.5-8.6 months), and median survival was 17 months (95% CI: 12.3-not recorded months). Grade 3/4 neutropenia occurred in 54% of patients, with febrile neutropenia in 24% of patients and 5% of cycles, but infections were rare. Stomatitis was frequent, grade 3 in 24% of patients and grade 4 in one patient (2%), but manageable. Diarrhoea was rare, grade 3 in 7% of patients and 1% of cycles. Other grade 3/4 nonhaematological toxicities were infrequent. In conclusion, this docetaxel/5-FU regimen is highly active and well tolerated in patients with anthracycline-pretreated metastatic breast cancer. The efficacy is particularly promising, as one-third of patients were either second-line and/or anthracycline-resistant/refractory.
本研究的目的是确定多西他赛联合持续输注5-氟尿嘧啶（5-FU）对先前接受过蒽环类药物治疗的转移性乳腺癌患者的疗效和安全性。共有41例经组织学证实为转移性乳腺癌且体能状态为0-2级、接受过至少一种含蒽环类药物方案治疗的患者，接受多西他赛85mg/m²，随后每3周持续输注5-FU 750mg/m²·天，共5天，最多进行8个周期。所有患者均接受皮质类固醇预处理，但未给予预防性集落刺激因子支持。最常见的转移部位是肝脏（61%）、骨骼（29%）和肺（29%）。所有41例患者均可评估毒性，30例符合条件且可评估疗效。符合方案组的客观缓解率为70.0%（95%CI：53.6-86.4%），意向性分析（ITT）人群的客观缓解率为53.7%（95%CI：38.4-68.9%）。对于ITT人群，中位缓解持续时间为8.4个月（95%CI：6.7-12.2个月），中位疾病进展时间为6.7个月（95%CI 5.5-8.6个月），中位生存期为17个月（95%CI：12.3-未记录个月）。54%的患者发生3/4级中性粒细胞减少，24%的患者出现发热性中性粒细胞减少，占周期数的5%，但感染罕见。口腔炎很常见，24%的患者为3级，1例患者（2%）为4级，但可控制。腹泻罕见，7%的患者为3级，占周期数的1%。其他3/4级非血液学毒性不常见。总之，这种多西他赛/5-FU方案对先前接受过蒽环类药物治疗的转移性乳腺癌患者具有高活性且耐受性良好。疗效特别令人鼓舞，因为三分之一的患者为二线治疗和/或对蒽环类药物耐药/难治。
