Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbazine in patients with metastatic malignant melanoma
Phase 3 study of docosahexaenoic acid-paclitaxel versus dacarbazine in patients with metastatic malignant melanoma
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DOI：
10.1093/annonc/mdq438
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发表时间：
2011-04-01
影响因子：
50.5
通讯作者：
Ernstoff, M.
中科院分区：
文献类型：
--
作者：
Bedikian, A. Y.;DeConti, R. C.;Ernstoff, M.
背景资料：二十二碳六烯酸-紫杉醇（DHA-紫杉醇，Taxoprexin（R））是通过将必需脂肪酸DHA共价结合到紫杉醇分子上制成的。DHA-紫杉醇的临床前研究已经证明了相对于紫杉醇的增加的活性和改善治疗比率的潜力。在本研究中，DHA-紫杉醇的疗效和毒性特征与dacarbazine.Methods：在这项研究中，393例转移性黑色素瘤化疗无效患者被随机分配接受DHA-紫杉醇，起始剂量为900 mg/m2，静脉注射，第1天，每3周一次，或达卡巴嗪，起始剂量为1000 mg/m2，静脉注射，第1天，每3周一次。研究的主要终点是总生存率（OS）的比较。结果：DHA-紫杉醇组和达卡巴嗪组患者的OS无显著差异。同样，两种药物之间的缓解率、缓解持续时间、进展时间和治疗失败时间也没有显着差异。两种药物的安全性结果与先前研究预测的结果一致。结论：DHA-紫杉醇并不优于达卡巴嗪上级。我们的结论是，进一步的研究与药物的每3周的时间表在黑色素瘤是没有必要的。
Background: Docosahexaenoic acid-paclitaxel (DHA-paclitaxel, Taxoprexin (R)) is made by covalently conjugating the essential fatty acid DHA to the paclitaxel molecule. Preclinical studies of DHA-paclitaxel have demonstrated increased activity relative to paclitaxel and the potential for an improved therapeutic ratio. In the present study, the efficacy and toxicity profiles of DHA-paclitaxel were compared with those of dacarbazine.Methods: In this study, 393 chemonaive patients with metastatic melanoma were randomly assigned to receive either DHA-paclitaxel at a starting dose of 900 mg/m(2) IV on day 1 every 3 weeks or dacarbazine at a starting dose of 1000 mg/m(2) IV on day 1 every 3 weeks. The primary end point of the study was the comparison of overall survival (OS).Results: No significant difference in OS was noted between patients in the DHA-paclitaxel and dacarbazine arms. Similarly, there were no significant differences in response rate, duration of response, time to progression, and time to treatment failure between the two drugs. Safety results of the two drugs were as predicted from prior studies. Myelosuppression was more common with DHA-paclitaxel.Conclusions: DHA-paclitaxel was not superior to dacarbazine. We conclude that further studies with the drug on an every 3-week schedule in melanoma are not warranted.