Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer
Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer
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DOI：
10.1200/jco.1996.14.6.1858
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发表时间：
1996-06-01
影响因子：
45.3
通讯作者：
Winograd, B
中科院分区：
文献类型：
--
作者：
Nabholtz, JM;Gelmon, K;Winograd, B
目的和方法：这项多中心研究的目的是比较两种不同剂量紫杉醇作为3小时输注给转移性乳腺癌（MBC）患者的治疗指数，这些患者对先前的化疗没有反应。共有471名MBC患者随机接受静脉注射紫杉醇，剂量为175或135 mg/m(2)，每3周一次。结果：高剂量（HD）紫杉醇比低剂量（LD）紫杉醇治疗效果更好：总有效率为29%比22% (P = 0.108)；完全缓解（CR）率，5% vs 2% (P = 0.088)；到疾病进展的中位时间为4.2个月对3.0个月（P = 0.027）；中位生存时间，11.7个月对10.5个月（P = .321），既往接触或耐药的患者与未接触过蒽环类药物的患者一样可能产生反应。治疗耐受性良好，治疗疗程数（中位数，6个vs 5个；范围，1到17个vs 1到18个），减少剂量的频率较低（14% vs 70%, P = 0.024），少量患者（n = 9或4%，n = 5或2%）因不良反应需要停药。中性粒细胞减少症和周围神经病变的发生率和严重程度与剂量有关。经过生命质量调整后的进展时间分析，HD组（175 mg/m(2)）仍然比LD组（135 mg/m(2)）具有优势。结论：本试验结果证实了紫杉醇治疗MBC的作用。175 mg/m(2)比135 mg/m(2)所观察到的疗效更好，这表明存在剂量效应关系。紫杉醇在蒽环类耐药患者中的临床活性尤其值得注意，紫杉醇在乳腺癌中的应用需要在使用联合化疗的大型试验中进一步评估，并涉及疾病早期阶段。(C)美国临床肿瘤学会1996。
Purpose and Methods: The objective of this multicenter study was to compare the therapeutic index of two different doses of paclitaxel given as a 3-hour infusion in patients with metastatic: breast cancer (MBC), who had failed to respond to previous chemotherapy. A total of 471 patients with MBC were randomized to receive intravenous paclitaxel at a dose of 175 or 135 mg/m(2) every 3 weeks.Results: Better treatment results were achieved with high-dose (HD) versus low-dose (LD) paclitaxel: overall response rate, 29% versus 22% (P = .108); complete response (CR) rate, 5% versus 2% (P = .088); median time to disease progression, 4.2 versus 3.0 months (P = .027); and median survival time, 11.7 versus 10.5 months (P = .321), patients previously exposed or resistant to anthracyclines were as likely to respond as those without such prior exposure. Treatment was well tolerated, as documented by the number of administered treatment courses (median, six v five; range, one to 17 v one to 18), the low frequency of dose reductions (14% v 70%, P = .024), and the small number of patients (n = 9 or 4% vn = 5 or 2%) who required treatment discontinuation for adverse reactions. The incidence and severity of neutropenia and peripheral neuropathy were dose-related. After quality-of-life-adjusted time-to-progression analysis, the HD arm (175 mg/m(2)) retained its advantage over the LD arm (135 mg/m(2)).Conclusion: The results of this trial substantiate the activity of paclitaxel in the treatment of MBC. The observed superior efficacy with a dose of 175 mg/m(2) over 135 mg/m(2) suggests a dose-effect relationship. The clinical activity in anthracycline-resistant patients is particularly noteworthy, Paclitaxel in breast cancer needs further evaluation in large trials that use combination chemotherapy and involve earlier disease stages. (C) 1996 by American Society of Clinical Oncology.