PHASE-II STUDY OF TAXOL IN PATIENTS WITH UNTREATED ADVANCED NON-SMALL-CELL LUNG-CANCER
PHASE-II STUDY OF TAXOL IN PATIENTS WITH UNTREATED ADVANCED NON-SMALL-CELL LUNG-CANCER
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DOI：
10.1093/jnci/85.5.384
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发表时间：
1993-03-03
期刊：
影响因子：
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通讯作者：
HONG, WK
中科院分区：
文献类型：
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作者：
MURPHY, WK;FOSSELLA, FV;HONG, WK
背景：紫杉醇是一种从短叶红豆杉树皮中提取的复杂植物产品（二萜），已证明对卵巢癌、乳腺癌、恶性黑色素瘤和急性髓性白血病具有显着的抗癌活性。由于 I 期和早期 II 期研究中的过敏反应，建议使用紫杉醇 24 小时输注预防性地塞米松、苯海拉明和西咪替丁。目的：在这项 II 期研究中，我们试图确定紫杉醇对从未接受过化疗的晚期（IIIB 或 IV 期）非小细胞肺癌患者的疗效和毒性。方法：患者并未因之前接受过手术或在研究开始前 4 周以上接受过放疗而被排除。在医院内以 200 mg/m2 的剂量静脉输注紫杉醇，持续 24 小时，每 3 周重复一次，前提是患者已从任何毒性作用中恢复。化疗前给予地塞米松、西咪替丁和苯海拉明以预防过敏反应。除非疾病快速进展，否则继续治疗至少两个疗程；如果没有观察到变化且没有发生 3 级或 4 级毒性反应，则继续治疗至少三个疗程。在最大缓解后继续治疗六个疗程，或在完全缓解后继续治疗两个疗程，但如果疾病进展则停止治疗。结果：在参与研究的 27 名患者中，有 25 名患者的毒性作用和反应可进行评估。一名患者出现过敏反应，但没有生命危险。总体答复率为 24%（1 名完全答复，5 名部分答复）。另外七名患者（28%）有轻微反应。粒细胞减少是剂量限制性毒性作用，118 个疗程中，有 8 个疗程出现中性粒细胞减少性发热。另外一名患者出现中性粒细胞减少性败血症并伴有低血压，但经过强化治疗后康复。结论：紫杉醇似乎具有抗非小细胞肺癌的活性。意义：现提出一项结合紫杉醇、依托泊苷和顺铂并使用造血刺激因子的 II 期研究。联合化疗的最佳剂量尚未确定。一个重要的考虑因素是紫杉醇与其他药物的潜在心脏作用。
Background: Taxol, a complex plant product (a diterpene) extracted from the bark of Taxus brevifolia, has demonstrated substantial anticancer activity in ovarian and breast cancers, malignant melanoma, and acute myelogenous leukemia. Due to allergic reactions in phase I and early phase II studies, use of a 24-hour infusion of taxol with prophylactic dexamethasone, diphenhydramine, and cimetidine has been recommended. Purpose: In this phase II study, we attempted to determine the efficacy and toxicity of taxol in patients with advanced (stage IIIB or IV) non-small-cell lung cancer who had never received chemotherapy. Methods: Patients were not excluded because of prior surgery or because of radiotherapy administered more than 4 weeks before study entry. Taxol was administered in the hospital at a dose of 200 mg/m2 as an intravenous infusion over 24 hours and repeated every 3 weeks, provided that patients had recovered from any toxic effects. Dexamethasone, cimetidine, and diphenhydramine were given before chemotherapy to prevent hypersensitivity reactions. Therapy was continued for at least two courses unless there was rapid disease progression and for at least three courses if no change was observed and no grade 3 or 4 toxic effects occurred. Treatment was continued for six more courses after maximum response or for two more courses after complete remission but was discontinued if disease progressed. Results: Of the 27 patients entered in the study, 25 were assessable for toxic effects and response. One patient had an allergic reaction that was not life threatening. The overall response rate was 24% (one complete response and five partial responses). An additional seven patients (28%) had minor responses. Granulocytopenia was the dose-limiting toxic effect, and neutropenic fever occurred in eight of 118 courses. One additional patient developed neutropenic sepsis with hypotension but recovered with intensive treatment. Conclusions: Taxol appears to have activity against non-small-cell carcinoma of the lung. Implications: A phase II study combining taxol, etoposide, and cisplatin and using hematopoietic stimulating factors is now proposed. The optimal dose for combination chemotherapy has yet to be determined. An important consideration is potential cardiac effects of taxol with other drugs.