Akerley W, Sikov W M, Cummings F, Safran H, Strenger R, Marchant D
Department of Medicine, Rhode Island Hospital, Brown University Oncology Group, Providence 02903, USA.
Semin Oncol. 1997 Oct;24(5 Suppl 17):S17-87-S17-90.
The optimal dose and schedule for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with advanced breast cancer are not known. Based on our phase I study in non-small cell lung cancer, in which the dose intensity of paclitaxel was successfully escalated by using a weekly schedule, we initiated a phase II study of weekly paclitaxel in previously untreated patients with metastatic breast cancer (MBC) and locally advanced breast cancer (LABC). Treatment consists of weekly paclitaxel 175 mg/m2 intravenously over 3 hours for 6 weeks, followed by a 2-week break. Doses are modified for neutropenia (absolute neutrophil count < 1,500/microL), bilirubin levels greater than 1.5 times normal, or greater than grade 1 neuropathy. Patients with MBC continue treatment until disease progression. Patients with LABC receive one to two cycles before proceeding to surgery if resectable. Thus far, 15 patients, eight with MBC and seven with LABC, are assessable for response and/or toxicity. Most patients have required dose modification, with median delivery of 75% (cycle 1) and 50% (cycle 2) of the planned dose of paclitaxel. Neutropenia has been the most common cause of dose reductions, although only one patient required treatment for neutropenic fever. Six patients have developed grade 2/3 peripheral sensory neuropathy, but with dose reductions many have continued treatment with stable or improving neurologic symptoms. Objective responses have been seen in 12 of 14 assessable patients, including six with MBC (one complete response, five partial responses) and six with LABC (two complete responses, four partial responses), for an overall response rate of 86% (95% confidence interval, 66% to 96%). All responding LABC patients have been rendered free from disease at surgery. These preliminary results are very encouraging. Accrual to the study continues.
用于治疗晚期乳腺癌患者的紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）的最佳剂量和给药方案尚不清楚。基于我们在非小细胞肺癌中的I期研究，其中通过每周给药方案成功提高了紫杉醇的剂量强度，我们启动了一项II期研究，对先前未接受治疗的转移性乳腺癌（MBC）和局部晚期乳腺癌（LABC）患者使用每周一次的紫杉醇进行治疗。治疗方案为每周静脉输注紫杉醇175mg/m²，持续3小时，共6周，随后休息2周。对于中性粒细胞减少（绝对中性粒细胞计数<1500/μL）、胆红素水平高于正常上限1.5倍或神经病变大于1级的情况，需调整剂量。MBC患者持续治疗直至疾病进展。LABC患者如果肿瘤可切除，则在手术前接受1至2个周期的治疗。迄今为止，15例患者（8例MBC患者和7例LABC患者）可评估疗效和/或毒性。大多数患者需要调整剂量，紫杉醇计划剂量的中位给药量为第1周期75%和第2周期50%。中性粒细胞减少一直是剂量减少的最常见原因，不过只有1例患者因中性粒细胞减少性发热需要治疗。6例患者出现2/3级周围感觉神经病变，但通过减少剂量，许多患者继续治疗，神经症状稳定或改善。14例可评估患者中有12例出现客观缓解，包括6例MBC患者（1例完全缓解，5例部分缓解）和6例LABC患者（2例完全缓解，4例部分缓解），总缓解率为86%（95%置信区间，66%至96%）。所有有反应的LABC患者在手术时均达到无病状态。这些初步结果非常令人鼓舞。该研究仍在继续入组患者。
