Aapro M, Bruno R
University Hospital, Geneva, Switzerland.
Eur J Cancer. 1995;31A Suppl 4:S7-10. doi: 10.1016/0959-8049(95)00360-u.
Docetaxel has been evaluated in six phase I studies involving a total of 234 patients with a wide variety of tumour types (50% had breast or ovarian cancer). The aims of these studies were to determine the optimal dosage schedule of docetaxel for use in subsequent phase II studies, and to characterise the pharmacokinetic and tolerability profiles of docetaxel. Intravenous (i.v.) doses of docetaxel (5-115 mg/m2) were administered in various treatment schedules for a total of 790 courses. Cycles were repeated every 2-3 weeks. Dose-dependent neutropenia was the major dose-limiting adverse effect of docetaxel. Other adverse events reported included hypersensitivity, fluid retention, skin reactions, asthenia and alopecia. Anaphylactoid reactions occurred rarely. No abnormal cardiac activity was detected, and neurological adverse events were mild. Docetaxel 100 mg/m2 administered as a 1 h i.v. infusion every 3 weeks combined acceptable tolerability with complete neutropenic recovery. This dosage schedule was thus considered to be optimal for further investigation in phase II studies.
多西他赛已在六项I期研究中进行了评估，共涉及234例患有多种肿瘤类型的患者（50%患有乳腺癌或卵巢癌）。这些研究的目的是确定多西他赛在后续II期研究中使用的最佳剂量方案，并描述多西他赛的药代动力学和耐受性特征。静脉注射（i.v.）多西他赛剂量为（5-115mg/m²），以各种治疗方案给药，共790个疗程。每2-3周重复一个周期。剂量依赖性中性粒细胞减少是多西他赛的主要剂量限制性不良反应。报告的其他不良事件包括超敏反应、液体潴留、皮肤反应、乏力和脱发。类过敏反应很少发生。未检测到异常心脏活动，神经学不良事件较轻。每3周静脉输注1小时给予100mg/m²多西他赛，耐受性良好，中性粒细胞完全恢复。因此，该剂量方案被认为是II期研究进一步调查的最佳方案。
