Weekly docetaxel in minimally pretreated cancer patients: A dose-escalation study focused on feasibility and cumulative toxicity of long-term administration
Weekly docetaxel in minimally pretreated cancer patients: A dose-escalation study focused on feasibility and cumulative toxicity of long-term administration
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DOI：
10.1023/a:1008399712913
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发表时间：
1999-06-01
影响因子：
50.5
通讯作者：
Pavlidis, N
中科院分区：
文献类型：
--
作者：
Briasoulis, E;Karavasilis, V;Pavlidis, N
背景：多西紫杉醇是一种具有令人印象深刻的临床活性的药物，但每三周给药一次的毒性相当差。因此，优化其临床应用是非常有必要的。这是一项每周一次多西紫杉醇的剂量递增研究，特别关注长期给药的可行性和累积毒性的表征。 患者和方法：26 名患者（11 名女性/15 名男性，中位年龄 56，范围 23-73）接受了每周 25-50 mg/m(2) 范围的治疗。该方案的剂量限制毒性被定义为任何> 2级抗增殖毒性作用，导致重新给药延迟> 2周，或任何> 2级器官特异性毒性。对患者的神经毒性进行临床和电生理监测。未给予长期皮质类固醇联合用药或预防性造血生长因子。结果：每位患者每周连续接受疗程的中位/平均次数为 8.5/8.7 个疗程。阻止按时给药的最大耐受剂量为 50 mg/m(2)。主要的累积毒性是轻微的液体潴留和流泪，随着治疗疗程次数的增加，这些毒性变得越来越明显。仅在 45 mg/m(2) 及更高剂量时观察到 2 级脱发和疲劳。在所有研究的剂量水平下均观察到活性。结论：多西紫杉醇每周长期给药是可行的，剂量高达 45 mg/m(2)/周，且毒性可接受。在此时间表中进一步的临床评估是合理的，并且建议将 40 mg/m(2)/周的多西他赛作为 II 期研究的活性剂量，具有最小的毒性。
Background: Docetaxel is an agent with impressive clinical activity but a rather poor profile of toxicity when given every three weeks. Therefore, optimisation of its clinical use is highly warranted. This is a dose-escalation study of weekly docetaxel particularly focused on the feasibility of long-term administration and characterisation of cumulative toxicity.Patients and methods: Twenty-six patients (11 female/15 male, median age 56, range 23-73) were treated over the range of 25-50 mg/m(2)/week. Dose-limiting toxicity for this schedule was defined as any grade > 2 antiproliferative toxic effect resulting in a > 2-week delay for re-administration of the drug, or any grade > 2 organ-specific toxicity. Patients were monitored clinically and electrophysiologically for neurotoxicity. No prolonged corticosteroid co-medication or prophylactic haematopoietic growth factors were given.Results: A median/mean number of 8.5/8.7 consecutive weekly courses were given per patient. The maximum tolerated dose that prevented on-schedule administration of the drug was 50 mg/m(2). The main cumulative toxicities were a mild fluid retention and dacryorrhea which became evident as the number of treatment courses increased. Grade 2 alopecia and fatigue were observed only at 45 mg/m(2) and higher. Activity was seen at all of the dose levels studied.Conclusions: Long-term weekly administration of docetaxel is feasible at doses up to 45 mg/m(2)/week with acceptable toxicity. Further clinical evaluation is justified at this schedule and 40 mg/m(2)/week of docetaxel is proposed for phase II studies as an active dose with minimal toxicity.