Rowinsky E K, Flood W A, Sartorius S E, Bowling M K, Wagner J, Ettinger D S
Johns Hopkins Oncology Center, Johns Hopkins Medical Institutions, Baltimore, MD 21287-8934, USA.
Semin Oncol. 1995 Aug;22(4 Suppl 9):48-54.
Preliminary results of a phase I study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), given by 3-hour infusion, followed by carboplatin in chemotherapy-naive patients with stage IV non-small cell lung cancer indicate that both agents can be combined at clinically relevant single-agent doses. The paclitaxel (mg/m2)/carboplatin area under the concentration-time curve (mg.min/mL) dose level of 225/7 is projected to be the maximally tolerated and recommended phase II dose level for future evaluations. Dose-limiting neutropenia, thrombocytopenia, and nausea and vomiting preclude treatment with carboplatin doses estimated to target an area under the concentration-time curve of 9 mg.min/mL when given with paclitaxel 225 mg/m2. The heterogeneous nature of the principal toxicities, as well as the ability to administer clinically relevant single-agent doses of both agents in combination, also indicate that further dose escalation of paclitaxel and carboplatin using hematopoietic growth factors would not be feasible. The preliminary antitumor activity noted to data, as well as the safety associated with the clinically relevant single-agent doses that can be given in combination, indicate that phase II/III evaluations of this regimen are warranted in patients with both advanced and early stage non-small cell lung cancer.
一项针对初治的IV期非小细胞肺癌患者的I期研究初步结果显示，采用3小时静脉输注给予紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿），随后给予卡铂，结果表明两种药物可按临床相关的单药剂量联合使用。紫杉醇（毫克/平方米）/卡铂浓度-时间曲线下面积（毫克·分钟/毫升）剂量水平为225/7，预计将是最大耐受剂量，并为未来评估推荐为II期剂量水平。剂量限制性中性粒细胞减少、血小板减少以及恶心和呕吐使得在给予225毫克/平方米紫杉醇时，无法使用估计靶向浓度-时间曲线下面积为9毫克·分钟/毫升的卡铂剂量进行治疗。主要毒性的异质性，以及联合给予两种药物临床相关单药剂量的能力，也表明使用造血生长因子进一步提高紫杉醇和卡铂的剂量不可行。目前观察到的初步抗肿瘤活性，以及与可联合给予的临床相关单药剂量相关的安全性，表明该方案在晚期和早期非小细胞肺癌患者中进行II/III期评估是有必要的。
