A Phase IIb Trial Assessing the Addition of Disulfiram to Chemotherapy for the Treatment of Metastatic Non‐Small Cell Lung Cancer. (16th March 2015)

• Record Type: Journal Article
• Authors: Nechushtan, Hovav; Hamamreh, Yousef; Nidal, Salim; Gotfried, Maya; Baron, Amichai; Shalev, Yossi Israeli; Nisman, Benjjamin; Peretz, Tamar; Peylan‐Ramu, Nili
• Is Part Of: Oncologist. Volume 20:Number 4(2015)
• Page Start: 366
• Page End: 367
• Publication Date: 2015-03-16
• Subjects: Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2014-0424
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: Disulfiram, an alcohol aversion agent, has been in use for >50 years. Numerous authors have reported an anticancer effect of this drug in vitro and in mouse models. More recently, several reports have claimed that disulfiram also possesses anti‐stem cell activity. We set out to obtain initial data regarding the safety of combining this drug with chemotherapy and the possible effectiveness of disulfiram in a combination regimen in non‐small cell lung cancer (NSCLC). Methods: This phase II, multicenter, randomized, double‐blinded study assessed the safety and efficacy of adding of disulfiram to cisplatin and vinorelbine for six cycles. Newly diagnosed NSCLC patients were recruited. Patients with either stage IV or what was considered at the time "wet IIIb" (since 2009, these patients have been considered stage IV) were recruited. The patients were treated with only chemotherapy, and none were treated with either surgery or chemoradiation. Disulfiram was administered at a dose of 40 mg three times daily. Results: Forty patients were treated for more than two cycles, half with and half without disulfiram, which was well tolerated. An increase in survival was noted for the experimental group (10 vs. 7.1 months). Interestingly, there were only two long‐term survivors, both in the disulfiram group. Conclusion: The addition of disulfiram to a combination regimen of cisplatin and vinorelbine was well tolerated and appeared to prolong survival in patients with newly diagnosed non‐small cell lung cancer. The results from this small study seem encouraging enough for assessment in larger trials. Disulfiram is an inexpensive and safe drug; if its addition to chemotherapy could be shown to prolong survival, an effective regimen could be established and used widely, even in resource‐poor countries. Abstract : 摘要 背景 . 双硫仑为酒精厌恶疗法的戒酒药物，迄今已应用50余年。 很多作者报告了该制剂在体外和小鼠模型中的抗癌作用。近年来，几项报告指出双硫仑还具有抗干细胞活性。本研究获得了非小细胞肺癌（NSCLC）中该药联合化疗的原始安全性数据，以及联合方案中双硫仑的可能疗效。 方法 . 本项多中心、随机、双盲II期研究评估了双硫仑联合顺铂与长春瑞滨治疗6周期的安全性和有效性。评估对象为新确诊的IV期或"wet IIIb"期（自2009年起，这些患者被视为IV期）NSCLC患者。这些患者仅接受化疗，无一例进行手术或化放疗。双硫仑给药剂次为40 mg，每日3次。 结果 . 40例患者接受了2个周期以上治疗，50%联合使用双硫仑，50%则未联合双硫仑。两种治疗均耐受良好。我们观察到研究组生存期延长（10个月vs. 7.1 个月）。值得注意的是，仅有2例长期生存患者，均在双硫仑组。 结论 . 对于新确诊的非小细胞肺癌患者，顺铂和长春瑞滨联合方案基础上添加双硫仑后，不但能够被很好地耐受，而且似乎可延长患者生存期。本次小规模研究结果很令人鼓舞，应在此基础上开展更大规模的试验。双硫仑费用不高，且安全性好；若在化疗中加入双硫仑证实具有生存获益，那么这种有效方案应该确立并广泛应用，包括资源贫乏的国家。 The Oncologist 2015;20:366–367