Kris M G, O'Connell J P, Gralla R J, Wertheim M S, Parente R M, Schiff P B, Young C W
Cancer Treat Rep. 1986 May;70(5):605-7.
Taxol is a unique plant product that promotes in vitro assembly of microtubules. In a phase I trial, adults with advanced solid tumors were given taxol (formulated with cremophor EL and dehydrated alcohol) as a 3-hour iv infusion every 21 days. The total dose administered ranged from 15 to 230 mg/m2 in nine escalation steps. Leukopenia, thrombocytopenia, nausea and vomiting, alopecia, stomatitis, transient rashes, increases in serum triglyceride levels, and hypersensitivity reactions were observed. Hypersensitivity reactions characterized by acute dyspnea, generalized erythema, and hypotension immediately following the initiation of the taxol infusion occurred in three of five patients receiving greater than or equal to 190 mg/m2 (18% of patients overall). No antitumor activity was observed. Hypersensitivity reactions constituted a treatment-limiting toxicity for this preparation of taxol given on this schedule over the dosage range examined. With the severity and unpredictability of the hypersensitivity reactions, further usage of taxol is not indicated with this drug formulation on this administration schedule. Further studies are warranted to uncover ways to permit the safe administration of taxol.
紫杉醇是一种独特的植物产物，可促进微管的体外组装。在一项I期试验中，患有晚期实体瘤的成年人每21天接受一次紫杉醇（用聚氧乙烯蓖麻油EL和无水乙醇配制）静脉输注，持续3小时。给药总剂量在九个递增步骤中从15至230mg/m²不等。观察到白细胞减少、血小板减少、恶心和呕吐、脱发、口腔炎、短暂皮疹、血清甘油三酯水平升高以及过敏反应。在接受大于或等于190mg/m²的五名患者中有三名（占所有患者的18%）在紫杉醇输注开始后立即出现以急性呼吸困难、全身性红斑和低血压为特征的过敏反应。未观察到抗肿瘤活性。在所研究的剂量范围内，按照该给药方案给予这种紫杉醇制剂时，过敏反应构成了一种限制治疗的毒性。鉴于过敏反应的严重性和不可预测性，按照该给药方案使用这种药物制剂时，不建议进一步使用紫杉醇。有必要进行进一步研究以发现允许安全使用紫杉醇的方法。
