Seidman A D, Hudis C A, Albanell J, Tong W, Tepler I, Currie V, Moynahan M E, Theodoulou M, Gollub M, Baselga J, Norton L
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
J Clin Oncol. 1998 Oct;16(10):3353-61. doi: 10.1200/JCO.1998.16.10.3353.
To evaluate the efficacy and toxicity of paclitaxel administered as a 1-hour infusion on weekly basis, without interruption, to patients with metastatic breast cancer who had received prior therapy.
Thirty patients with metastatic breast cancer received sustained weekly paclitaxel therapy at an initial dose of 100 mg/m2 until disease progression. Prior therapy included adjuvant only (n=17), metastatic only (n=7), or both (n=6). Eighteen patients had received prior anthracycline therapy, 12 of whom had demonstrated progression of disease within 12 months of it. All patients were assessable for efficacy; 29 patients were assessable for toxicity. Pharmacokinetic studies of paclitaxel were also performed.
A total of 469 weekly paclitaxel infusions were administered to 30 patients (median, 14 infusions/patient). The median delivered dose-intensity was 91 mg/m2/wk (range, 80 to 108). The overall response rate was 53% (95% confidence interval [CI], 34% to 72%), with 10% complete responses (CRs) and 43% partial responses (PRs). Median response duration was 7.5 months (range, 2 to 11+). Responses were observed in nine of 18 (50%) patients with prior anthracycline therapy, including six of 12 (50%) with disease progression on anthracycline within 1 year (three of four within 6 months). Therapy was well tolerated and remarkable for a lack of overall and cumulative myelosuppression. Grade 3/4 neutropenia occurred in four patients; febrile neutropenia was not observed. Peripheral neuropathy prohibited dose escalation above 100 mg/m2, and grade 3 neuropathy was observed in two of 21 patients at < or = 100 mg/m2.
Weekly paclitaxel therapy is active and well tolerated in patients with metastatic breast cancer. Weekly therapy should be considered as a current clinical option for these patients and should be incorporated into future comparative clinical trials.
评估对接受过先前治疗的转移性乳腺癌患者每周进行1小时静脉输注紫杉醇且不间断给药的疗效和毒性。
30例转移性乳腺癌患者接受持续的每周紫杉醇治疗，初始剂量为100mg/m²，直至疾病进展。先前治疗包括仅辅助治疗（n = 17）、仅转移性治疗（n = 7）或两者皆有（n = 6）。18例患者接受过先前的蒽环类药物治疗，其中12例在接受该治疗的12个月内出现疾病进展。所有患者均可评估疗效；29例患者可评估毒性。还进行了紫杉醇的药代动力学研究。
30例患者共接受了469次每周紫杉醇输注（中位数，每位患者14次输注）。中位给药剂量强度为91mg/m²/周（范围，80至108）。总体缓解率为53%（95%置信区间[CI]，34%至72%），其中完全缓解（CR）率为10%，部分缓解（PR）率为43%。中位缓解持续时间为7.5个月（范围，2至11+）。在18例接受过先前蒽环类药物治疗的患者中有9例（50%）出现缓解，包括12例在1年内蒽环类药物治疗期间疾病进展的患者中的6例（50%）（4例在6个月内有3例）。治疗耐受性良好，且明显缺乏总体和累积性骨髓抑制。4例患者出现3/4级中性粒细胞减少；未观察到发热性中性粒细胞减少。周围神经病变禁止将剂量增至100mg/m²以上，在21例剂量≤100mg/m²的患者中有2例出现3级神经病变。
每周紫杉醇治疗对转移性乳腺癌患者有效且耐受性良好。每周治疗应被视为这些患者当前的临床选择，并应纳入未来的比较性临床试验。
