Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma
Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma
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DOI：
10.1200/jco.1999.17.8.2309
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发表时间：
1999-08-01
影响因子：
45.3
通讯作者：
Hong, WK
中科院分区：
文献类型：
--
作者：
Glisson, BS;Kurie, JM;Hong, WK
目的：在广泛性小细胞肺癌患者中进行顺铂、依托泊苷和紫杉醇联合治疗的 I 期试验，随后进行 II 期试验，以确定最大耐受剂量 (MTD)、表征毒性并估计疗效和中位生存率。患者和方法：1993 年 10 月至 1997 年 4 月期间对 41 名患者进行了治疗。初始队列的剂量为顺铂 75 mg/m(2)第 1 天，依托泊苷 80 mg/m(2)/d，第 1 至 3 天，紫杉醇 130 mg/m(2)，第 1 天，持续 3 小时。每 3 周重复一次周期，最多六个周期。前 6 名患者达到了 MTD。在这 6 名患者和接下来进入 II 期试验的 35 名患者中，评估了反应和生存率。结果：在初始剂量水平下，6 名患者中的 1 名出现发热性中性粒细胞减少症，6 名患者中的 5 名实现了目标中性粒细胞减少症（最低绝对粒细胞计数，100 至 1,000/1 μL），没有任何其他剂量限制性毒性，将该水平定义为 MTD。在等于或低于 MTD 的 188 个总疗程中，有 88 个疗程（47%）观察到 4 级中性粒细胞减少症。 188 个疗程中，只有 17 个（9%）出现中性粒细胞减少症并伴有发热，但有两名患者出现致命的中性粒细胞减少性败血症。在 188 个总疗程中，有 10 个疗程（5%）观察到大于 2 级的非血液学毒性，其中疲劳、周围神经病变和恶心/呕吐最常见。 38 名可评估患者的总体客观缓解率为 90%：6 名完全缓解 (16%) 和 28 名部分缓解 (74%)。中位无进展生存期和总生存期分别为 31 周和 47 周。 结论：顺铂、依托泊苷和紫杉醇联合用药产生的反应和生存率与其他组合相似，并且耐受性良好。
Purpose: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates.Patients and Methods: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on day 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated.Results: Al the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/1 mu L) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia wets associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses (74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively.Conclusion: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.