Digestive, Thoracic and Oncologic Unit, Department of Diagnostic and Interventional Radiology, University Hospital of Dijon, 14, rue Paul Gaffarel, Dijon, 21000, France.
Cardiovasc Intervent Radiol. 2013 Aug;36(4):1039-46. doi: 10.1007/s00270-012-0532-8. Epub 2012 Dec 8.
There is still no consensus about the best chemotherapeutic agent for transarterial chemoembolization (TACE). A recent in vitro study demonstrated that idarubicin, an anthracycline, was by far the most cytotoxic drug on human hepatocellular carcinoma (HCC) cell lines. Idarubicin is much more lipophilic than doxorubicin, leading to higher cell penetration through lipidic membranes and greater accumulation of the drug in the lipiodol. Furthermore, idarubicin has the ability to overcome multidrug resistance. Therefore, we designed this pilot human study to evaluate the safety and efficacy of lipiodol TACE using idarubicin.
In 21 consecutive patients treated by lipiodol TACE with idarubicin (10 mg) for HCC, safety data, tumor response (Response Evaluation Criteria in Solid Tumors, mRECIST), time to treatment failure (TTTF), and overall survival were evaluated.
Postembolization syndrome was observed after 30.9% (17 of 55) of sessions. No patient died from a TACE-related complication. No hematological grade 3-5 adverse event was observed. At least one grade 3 or higher adverse event occurred in 19% (4 of 21) of patients. On imaging, no progression was encountered; four patients (24%) exhibited stable disease, 12 (57%) exhibited a partial response, and five (19%) exhibited a complete response. Median TTTF was 16.7 months (Kaplan-Meier analysis). At 6 months, 94.7% (95% confidence interval [CI] 68.1-99.2) of patients did not reach treatment failure, whereas treatment failure was not reached in 50.6% (95% CI 21.6-73.9) of patients at 1 year. Overall survival was 83.5% (95% CI 57-94.4) at 1 year.
Idarubicin seems safe and effective in lipiodol TACE of HCC. This warrants further study to determine the potential of this drug to replace doxorubicin for TACE.
经动脉化疗栓塞(TACE)的最佳化疗药物仍无定论。最近的一项体外研究表明,柔红霉素(一种蒽环类抗生素)是迄今为止对人肝癌(HCC)细胞系最具细胞毒性的药物。柔红霉素比阿霉素更亲脂,可使药物通过脂膜更深入地渗透,使药物在碘油中的蓄积量更大。此外,柔红霉素具有克服多药耐药性的能力。因此,我们设计了这项前瞻性人体研究,以评估使用柔红霉素的碘油 TACE 的安全性和疗效。
21 例 HCC 患者连续接受碘油 TACE 联合柔红霉素(10mg)治疗,评估安全性数据、肿瘤反应(实体瘤反应评价标准,mRECIST)、治疗失败时间(TTTF)和总生存期。
55 次治疗中有 30.9%(17/55)出现栓塞后综合征。无患者因 TACE 相关并发症而死亡。未观察到血液学 3-5 级不良事件。19%(4/21)的患者至少发生 1 次 3 级或更高级别的不良事件。影像学上未见进展,4 例(24%)患者疾病稳定,12 例(57%)患者部分缓解,5 例(19%)患者完全缓解。中位 TTTF 为 16.7 个月(Kaplan-Meier 分析)。6 个月时,94.7%(95%置信区间[CI]68.1-99.2)的患者未达到治疗失败,而 1 年时,50.6%(95%CI21.6-73.9)的患者未达到治疗失败。1 年总生存率为 83.5%(95%CI57-94.4)。
柔红霉素在 HCC 的碘油 TACE 中似乎是安全有效的。这需要进一步的研究来确定这种药物替代阿霉素用于 TACE 的潜力。