Patrikidou Anna, Sinapi Isabelle, Regnault Hélène, Fayard Florence, Bouattour Mohamed, Fartoux Laetitia, Faivre Sandrine, Malka David, Ducreux Michel, Boige Valerie
Department of Oncologic Medicine, Gustave-Roussy, Villejuif, France.
Invest New Drugs. 2014 Oct;32(5):1028-35. doi: 10.1007/s10637-014-0100-y. Epub 2014 Apr 22.
Sorafenib is the only systemic treatment that has shown a significant benefit in overall survival (OS) and in progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients. No standard of care currently exists for second-line treatment. The association of Gemcitabine-Oxaliplatine (GEMOX) has shown efficacy in the first-line setting. The aim of this study was to evaluate the efficacy of GEMOX after failure of at least one line of anti-angiogenic (AA) therapy.
We performed a multicenter retrospective analysis of advanced HCC patients that received GEMOX chemotherapy after progression on at least one line of AA therapy.
We analyzed a total of 40 patients that received a median of 7 cycles of GEMOX over a 6-year period. Grade 3/4 toxicity was observed in 25 % of patients, mainly neurotoxicity, thrombocytopenia and neutropenia in 12.5 %, 5 % and 5 % of patients respectively. Grade <3 toxicity was mainly hematological and neurotoxicity. In the sub-cohort of 35 patients evaluable for response, partial response was observed in 20 % of patients, while 46 % had stable disease. Median OS was 8.3 months, with a 6-month OS rate of 59 %. Median PFS was 3.1 months. Prognostic factors for OS in univariable analysis were the performance status and AFP levels at GEMOX start, and the BCLC score at diagnosis. None of these factors were prognostic for PFS or tumor response.
The GEMOX schedule seems to show clinical activity and an acceptable toxicity profile in advanced HCC patients who progressed after anti-angiogenic treatment. The observed median OS of over 8 months is encouraging in this population of heavily pretreated patients. These results would merit confirmation in a prospective randomized study.
索拉非尼是唯一一种在晚期肝细胞癌（HCC）患者的总生存期（OS）和无进展生存期（PFS）方面显示出显著益处的全身治疗药物。目前二线治疗尚无标准治疗方案。吉西他滨 - 奥沙利铂（GEMOX）联合方案在一线治疗中已显示出疗效。本研究的目的是评估在至少一线抗血管生成（AA）治疗失败后GEMOX的疗效。
我们对在至少一线AA治疗进展后接受GEMOX化疗的晚期HCC患者进行了多中心回顾性分析。
我们共分析了40例患者，这些患者在6年期间接受GEMOX化疗的中位周期数为7个周期。25%的患者观察到3/4级毒性，主要为神经毒性、血小板减少症和中性粒细胞减少症，分别发生在12.5%、5%和5%的患者中。<3级毒性主要为血液学和神经毒性。在可评估疗效的35例患者亚组中，20%的患者观察到部分缓解，而46%的患者病情稳定。中位OS为8.3个月，6个月OS率为59%。中位PFS为3.1个月。单因素分析中OS的预后因素为开始GEMOX治疗时的体能状态和甲胎蛋白水平，以及诊断时的BCLC评分。这些因素均不是PFS或肿瘤反应的预后因素。
GEMOX方案在抗血管生成治疗后进展的晚期HCC患者中似乎显示出临床活性和可接受的毒性特征。在这群经过大量预处理的患者中，观察到的中位OS超过8个月令人鼓舞。这些结果值得在前瞻性随机研究中得到证实。
