Lombardi Davide, Crivellari Diana, Scuderi Cristina, Magri Maria Donatella, Spazzapan Simon, Sorio Roberto, Di Lauro Vincenzo, Scalone Simona, Veronesi Andrea
Division of Medical Oncology C, Centro di Riferimento Oncologico, Aviano, Italy.
Tumori. 2004 May-Jun;90(3):285-8. doi: 10.1177/030089160409000304.
A dose-dense therapy with weekly paclitaxel given as a 1-hr infusion yielded a 53% overall response rate in breast cancer patients resistant to anthracyclines, with a remarkable lack of neutropenia (Seidman, 1998). We performed a monoinstitutional phase II trial in order to confirm these interesting results.
Eligibility criteria included advanced breast cancer and no taxane pretreatment. Paclitaxel was administered weekly at the dose of 90 mg/m2 (60 mg/m2 in patients at high risk of toxicity) by 1-hr i.v. infusion. Fifty-eight patients entered the trial. Median age was 54 years (range, 38-72). Performance status was good (median 1; range, 0-2). Fifty-two patients were pretreated with anthracyclines.
A total of 1,004 weekly paclitaxel infusions were administered (median, 19 per patient; range, 4-43). The median delivered dose intensity was 67.4 mg/m2/week (range, 43-86). Twenty-eight of the 58 assessable patients obtained an objective response (48%), 15 had stable disease (26%) and 15 progressed (26%). The overall response rate was 48% (95% confidence interval, 35-61%) with 5 complete responses (8%). In anthracycline-pretreated patients, 23/52 (44%) responses were observed. Median duration of response was 5 months (range, 3-27). Toxicity was acceptable apart from a case of pulmonary embolism in a 70-year-old patient, 1 case of congestive heart failure in an anthracycline-pretreated patient aged 64, and 9 cases of G3 neutropenia. Peripheral neuropathy was observed in 38 patients (64%), usually of a mild grade; alopecia in 45 patients (78%) and onychopathy in 16 (28%), usually of a mild grade apart from 2 cases requiring treatment interruption. Tachycardia and atrial fibrillation occurred in a 55-year-old woman.
Our data seem to confirm the activity and safety of this approach even in a heavily pretreated population of patients. Its combination with other active drugs needs to be further investigated in clinical trials.
对于对蒽环类药物耐药的乳腺癌患者，采用每周1小时静脉输注紫杉醇的剂量密集疗法，总缓解率为53%，且明显缺乏中性粒细胞减少症（Seidman，1998年）。我们开展了一项单机构II期试验以证实这些有趣的结果。
纳入标准包括晚期乳腺癌且未接受过紫杉烷预处理。紫杉醇以90mg/m²的剂量（毒性高危患者为60mg/m²）每周通过1小时静脉输注给药。58名患者进入试验。中位年龄为54岁（范围38 - 72岁）。体能状态良好（中位值为1；范围0 - 2）。52名患者曾接受过蒽环类药物治疗。
共进行了1004次每周一次的紫杉醇输注（中位值为每位患者19次；范围4 - 43次）。中位给药剂量强度为67.4mg/m²/周（范围43 - 86）。58名可评估患者中，28名获得客观缓解（48%），15名疾病稳定（26%），15名病情进展（26%）。总缓解率为48%（95%置信区间35 - 61%），其中5例完全缓解（8%）。在接受过蒽环类药物治疗的患者中，观察到23/52（44%）例缓解。中位缓解持续时间为5个月（范围3 - 27个月）。除了1例70岁患者发生肺栓塞、1例64岁接受过蒽环类药物治疗的患者发生充血性心力衰竭以及9例3级中性粒细胞减少症外，毒性是可接受的。38名患者（64%）出现周围神经病变，通常为轻度；45名患者（78%）出现脱发，16名患者（28%）出现甲病，除2例需要中断治疗外，通常为轻度。一名55岁女性出现心动过速和心房颤动。
我们的数据似乎证实了这种方法在即使是经过大量预处理的患者群体中的活性和安全性。其与其他活性药物的联合应用需要在临床试验中进一步研究。
