Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer
Phase I and pharmacological study of paclitaxel given over 3 h with cisplatin for advanced non-small cell lung cancer
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DOI：
10.1093/jjco/hye022
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发表时间：
2001-03-01
影响因子：
2.4
通讯作者：
Saijo, N
中科院分区：
文献类型：
--
作者：
Kurata, T;Tamura, T;Saijo, N
背景资料：为了确定紫杉醇联合顺铂3 h的毒性和最大耐受剂量，确定这两种药物的药代动力学特征并观察其抗肿瘤活性，我们进行了非小细胞肺癌的联合I期研究。方法：患者在3小时内接受150-210 mg/m2的紫杉醇剂量，并在紫杉醇输注结束后2小时接受60-80 mg/m2的顺铂剂量，1小时输注。共入组了25例既往未经治疗的非小细胞肺癌患者。粒细胞减少症是最常见的遗传毒性，最突出的非血液学毒性是感觉显性神经病变。在紫杉醇210 mg/m2和顺铂60 mg/m2（被认为是最大耐受剂量）剂量下，6例患者中有2例出现剂量限制性毒性（白细胞减少症、感染和神经病变）。在24例可评价患者中有7例部分缓解，总体缓解率为29%。中位生存期为341天，1年生存率为45.8%。由于本研究中紫杉醇的药代动力学参数与我们以前的单药研究结果一致，我们发现紫杉醇和顺铂之间没有明显的药物相互作用。结论：进一步研究的推荐剂量确定为紫杉醇180 mg/m2和顺铂80 mg/m2。这是一种耐受性良好且有效的非小细胞肺癌治疗方案。鉴于有希望的生存结局，需要在前瞻性随机试验中与其他方案进行进一步评价。
Background: To establish the toxicities and maximum tolerated dose of paclitaxel given over 3 h in combination with cisplatin, to determine the pharmacokinetic profiles of these two drugs and to observe their antitumor activity, we conducted a combination phase I study in non-small cell lung cancer.Methods: Patients received paclitaxel doses of 150-210 mg/m(2) given over 3 h and cisplatin doses of 60-80 mg/m(2) as a 1 h infusion 2 h after the end of the paclitaxel infusion.Results: A total of 25 patients with previously untreated non-small cell lung cancer were enrolled. Granulocytopenia was the most frequent hernatological toxicity and the most prominent non-hematological toxicity was sensory dominant neuropathy. Two of six patients experienced dose limiting toxicities (leukopenia, infection and neuropathy) at a dose of paclitaxel 210 mg/m2 and cisplatin 60 mg/m(2), which was considered the maximum tolerated dose. There were seven partial responses among 24 evaluable patients, for an overall response rate of 29%. The median survival time was 341 days and the 1 year survival rate was 45.8%. As the paclitaxel pharmacokinetic parameters in this study were consistent with those of our previous single agent study, we found no significant drug-drug interaction between the 3 h infusion paclitaxel and cisplatin.Conclusion: The recommended doses for further study are determined to be paclitaxel 180 mg/m(2) and cisplatin 80 mg/m(2). This is a well-tolerated and active regimen for non-small cell lung cancer. In view of the promising survival outcome, further evaluation in prospective randomized trials versus other regimens is warranted.