Sørensen J B, Wedervang K, Dombernowsky P
Finsen Center, Copenhagen University Hospital, Denmark.
Semin Oncol. 1997 Aug;24(4 Suppl 12):S12-18-S12-20.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin are cytotoxic drugs active against non-small cell lung cancer (NSCLC) that possess additive cytotoxicity in animal tumors. Paclitaxel and cisplatin are active in patients with advanced NSCLC when given on a 3-weekly schedule. In an attempt to increase activity, we designed a phase II study with a biweekly schedule. Paclitaxel 110 mg/m2 was given by 3-hour intravenous infusion, followed by cisplatin 60 mg/m2 via intravenous infusion. Treatment was scheduled every 2 weeks. Of the 42 patients treated, 19 were men and 23 were women, with a median age of 54 years (range, 31 to 69 years). Four patients had stage IIIA NSCLC, 18 stage IIIB, and 20 stage IV. Median World Health Organization performance status was 1 (range, 0 to 2), and adenocarcinoma was the most common histology (52%). A median of nine cycles was administered (range, one to 24 cycles), with more than 360 cycles administered. Rates of frequency of World Health Organization grade 3 or 4 toxicities were as follows: neutropenia, 20%; thrombocytopenia, 2%; nausea/vomiting, 7% (despite prophylactic treatment with 5-HT3 receptor antagonists plus prednisolone); neurotoxicity, 2%; and nephrotoxicity, 2%. There were three septicemic episodes, no bleeding episodes, and no toxic deaths. Dose reduction was performed in 15 patients (36%), due to nephrotoxicity in 14 cases. Treatment delay was necessary in 23 patients (55%), most often due to neutropenia (nine cases). Forty patients are currently evaluable for response, with two complete and 15 partial responses (overall response rate, 43%; 95% confidence limits, 27% to 59%). Median response duration was 31 weeks (range, 9 to 85 weeks). The biweekly schedule of paclitaxel plus cisplatin has noteworthy activity in patients with NSCLC. A relatively large fraction of patients required either dose reduction and/or treatment delay, but World Health Organization grade 3 or 4 toxicity was rare, apart from the neutropenia that caused only a few septicemic episodes.
紫杉醇（泰素；百时美施贵宝公司，新泽西州普林斯顿）和顺铂是对非小细胞肺癌（NSCLC）有效的细胞毒性药物，在动物肿瘤中具有相加的细胞毒性。紫杉醇和顺铂按每3周一次的方案给药时，对晚期NSCLC患者有效。为了提高疗效，我们设计了一项采用每2周一次方案的II期研究。紫杉醇110mg/m²通过3小时静脉输注给药，随后顺铂60mg/m²通过静脉输注给药。治疗计划每2周进行一次。在接受治疗的42例患者中，19例为男性，23例为女性，中位年龄为54岁（范围31至69岁）。4例患者为IIIA期NSCLC，18例为IIIB期，20例为IV期。世界卫生组织体能状态中位数为1（范围0至2），腺癌是最常见的组织学类型（52%）。中位给药周期数为9个周期（范围1至24个周期），给药周期数超过360个。世界卫生组织3级或4级毒性的发生率如下：中性粒细胞减少，20%；血小板减少，2%；恶心/呕吐，7%（尽管使用5-羟色胺3受体拮抗剂加泼尼松龙进行预防性治疗）；神经毒性，2%；肾毒性，2%。有3次败血症发作，无出血发作，无毒性死亡。15例患者（36%）进行了剂量减少，其中14例是由于肾毒性。23例患者（55%）需要治疗延迟，最常见的原因是中性粒细胞减少（9例）。目前40例患者可评估疗效，2例完全缓解，15例部分缓解（总缓解率43%；95%置信区间，27%至59%）。中位缓解持续时间为31周（范围9至85周）。紫杉醇加顺铂每2周一次的方案在NSCLC患者中具有显著疗效。相当一部分患者需要进行剂量减少和/或治疗延迟，但除了导致少数败血症发作的中性粒细胞减少外，世界卫生组织3级或4级毒性很少见。
