PLATINUM ORAL ETOPOSIDE THERAPY IN NON-SMALL-CELL LUNG-CANCER
PLATINUM ORAL ETOPOSIDE THERAPY IN NON-SMALL-CELL LUNG-CANCER
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DOI：
10.1159/000227113
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发表时间：
1992-07-01
期刊：
影响因子：
3.5
通讯作者：
SHINKAI
中科院分区：
文献类型：
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作者：
FURUSE, K;HARA;SHINKAI
长期每日口服依托泊苷治疗肺癌已观察到令人鼓舞的缓解率。 EP（依托泊苷/顺铂）已被用于治疗非小细胞肺癌（NSCLC），尽管事实上依托泊苷仅表现出一定程度的对抗该疾病的活性，但其原因是顺铂/依托泊苷协同作用的临床前建议以及联合治疗小细胞肺癌（SCLC）的成功结果。我们评估了长期每日口服依托泊苷方案联合顺铂治疗 NSCLC。一个疗程包括第 1 天的顺铂和第 1 天至第 2 天的依托泊苷 1。从第 29 天开始重复该疗程。我们得出的结论是，该方案中的最大耐受剂量为 50 mg/m2/天口服依托泊苷，持续 21 天，加上第 1 天静脉注射 80 mg/m2 顺铂。主要的剂量限制性毒性作用是骨髓抑制，粘膜炎也对某些患者有显着意义。在这项对 22 名患者（18 名可评估）进行的 I 期研究中，我们观察到 4 名患者出现部分缓解 (PR)，其中 1 名患有子宫癌和 SCLC，2 名患有鳞状细胞肺癌。然后，我们针对晚期 NSCLC 患者设计了一项 II 期试点研究。推荐的治疗方案是静脉注射 80 mg/m2。第 1 天顺铂加 40 mg/m2/天口服依托泊苷，连续 21 天。在 13 名可评估患者中，4 名（30.8%）患者观察到 PR，其中 2 名腺癌患者和 2 名鳞状细胞癌患者。所有副作用均不严重或危及生命。几乎所有预计剂量都已注射，但延迟了 7-10 天。在这项试点II期研究中，晚期NSCLC的缓解率超过30%。未来的研究应将长期口服依托泊苷与放射治疗或手术结合起来治疗 III 期 NSCLC。
Encouraging response rates have been observed with long-term daily administration of oral etoposide to treat lung cancer. Reasons why EP (etoposide/cisplatin) has been used to treat non-small cell lung cancer (NSCLC), despite the fact that etoposide has demonstrated only a modest degree of activity against this disease, are preclinical suggestions of cisplatin/etoposide synergism and successful results for the combination in treating small cell lung cancer (SCLC). We evaluated a long-term daily oral etoposide regimen in combination with cisplatin for NSCLC. One course consisted of cisplatin on day 1 and etoposide from day 1 through day 2 1. The course was repeated, beginning at day 29. We concluded that the maximum tolerated dose in this schedule was 50 mg/m2/day oral etoposide for 21 days plus 80 mg/m2 intravenous (i.v.) cisplatin on day 1. The major dose-limiting toxic effect was myelosuppression, and mucositis was also significant in some patients. During this phase I study of 22 patients (18 evaluable), we observed partial responses (PRs) in 4 patients, 1 each with uterine cancer and SCLC, and 2 with squamous cell lung cancers. We then designed a phase II pilot study in patients with advanced NSCLC. The recommended treatment schedule is 80 mg/m2 i.v. cisplatin on day 1 plus 40 mg/m2/day oral etoposide for 21 consecutive days. Of the 13 evaluable patients, PRs were observed in 4 (30.8%), in 2 patients with adenocarcinoma and 2 with squamous cell carcinoma. None of the side effects were severe or life-threatening. Nearly all of the projected doses were given, with delays of 7-10 days. In this pilot phase II study, the response rate of advanced NSCLC was above 30%. Future studies should combine long-term administration of oral etoposide with radiation therapy or surgery to treat stage III NSCLC.