A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results
A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results
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DOI：
10.1007/s12032-010-9700-3
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发表时间：
2011-12-01
期刊：
影响因子：
3.4
通讯作者：
Duenas-Gonzalez, Alfonso
中科院分区：
文献类型：
--
作者：
Coronel, Jaime;Cetina, Lucely;Duenas-Gonzalez, Alfonso
使用DNA甲基化和组蛋白去乙酰化酶抑制剂逆转表观遗传畸变可能对宫颈癌具有治疗价值。这是一项肼苯哒嗪和丙戊酸盐（HV）联合顺铂拓扑替康治疗晚期宫颈癌的随机、III期、安慰剂对照研究。患者在化疗前一周开始接受肼屈嗪182 mg（快速乙酰化）或83 mg（缓慢乙酰化），丙戊酸盐30 mg/kg，并持续至疾病进展。评价了缓解、毒性和PFS，纳入了36例患者（17例CT + HV和19例CT + PLA）。中位周期数为6个。CT + HV有4例PR，CT + PLA有1例PR。分别有5名（29%）和6名（32%）患者病情稳定，而8名（47%）和12名（63%）患者显示进展（P = 0.27）。中位随访时间为7个月（1-22）时，CT + PLA的中位PFS为6个月，CT + HV为10个月（P = 0.0384，双尾）。虽然是初步的，但这项研究代表了第一项随机临床试验，证明表观遗传治疗在宫颈癌无进展生存率方面优于目前标准的联合化疗。与本试验的反应和存活率相关的分子学尚待分析。
The reversing of epigenetic aberrations using the inhibitors of DNA methylation and histone deacetylases may have therapeutic value in cervical cancer. This is a randomized phase III, placebo-controlled study of hydralazine and valproate (HV) added to cisplatin topotecan in advanced cervical cancer. Patients received hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression. Response, toxicity, and PFS were evaluated, and 36 patients (17 CT + HV and 19 CT + PLA) were included. The median number of cycles was 6. There were four PRs to CT + HV and one in CT + PLA. Stable disease in five (29%) and six (32%) patients, respectively, whereas eight (47%) and 12 (63%) showed progression (P = 0.27). At a median follow-up time of 7 months (1-22), the median PFS is 6 months for CT + PLA and 10 months for CT + HV (P = 0.0384, two tailed). Although preliminary, this study represents the first randomized clinical trial to demonstrate a significant advantage in progression-free survival for epigenetic therapy over one of the current standard combination chemotherapy in cervical cancer. Molecular correlates with response and survival from this trial are pending to analyze.