Institut du Cancer de Montpellier (ICM), Université de Montpellier, Montpellier, France.
Centre Hospitalier Universitaire de Montpellier, Université de Montpellier, Montpellier, France.
Br J Cancer. 2019 Apr;120(9):896-902. doi: 10.1038/s41416-019-0443-4. Epub 2019 Apr 4.
Sorafenib remains one major first-line therapeutic options for advanced hepatocellular carcinoma (aHCC), with modest efficacy. We investigated the addition of gemcitabine and oxaliplatin (GEMOX) to sorafenib in aHCC patients.
Our multicentre phase II trial randomised aHCC first-line patients to sorafenib (400 mg BID) or sorafenib-GEMOX every 2 weeks (1000 mg/m gemcitabine; 100 mg/m oxaliplatin). Primary endpoint was the 4-month progression-free survival (PFS) rate.
Ninety-four patients were randomised (sorafenib-GEMOX: n = 48; sorafenib: n = 46). Median age was 64 years, PS 0 (69%) or 1 (31%), 63% patients had cirrhosis, 29% portal vein thrombosis and 70% extra-hepatic disease. Median duration of sorafenib treatment was 4 months (1-51); median number of GEMOX cycles was 7 (1-16). The 4-month PFS rates were 64% and 61% in the sorafenib-GEMOX and sorafenib arms, respectively; median PFS and OS were 6.2 (95% CI: 3.8-6.8) and 13.5 (7.5-16.2) months, and 4.6 (3.9-6.2) months and 14.8 (12.2-22.2), respectively. The ORR/DCR were 9%/70% and 15%/77% in the sorafenib-GEMOX and sorafenib alone arms, respectively. Main toxicities were (sorafenib-GEMOX/sorafenib) neutropenia (23%/0), thrombocytopenia (33%/0), diarrhoea (18%/9), peripheral neuropathy (5%/0) and hand-foot syndrome (5%/18).
Addition of GEMOX had an inpact on ORR and was well-tolerated as frontline systemic therapy. The benefit on PFS seems moderate; no subsequent study was planned.
索拉非尼仍然是晚期肝细胞癌（aHCC）的主要一线治疗选择之一，疗效适度。我们研究了吉西他滨和奥沙利铂（GEMOX）联合索拉非尼在 HCC 患者中的应用。
我们的多中心 II 期试验将 HCC 一线患者随机分为索拉非尼（400mg BID）或索拉非尼-GEMOX 每 2 周（1000mg/m 吉西他滨；100mg/m 奥沙利铂）。主要终点是 4 个月无进展生存期（PFS）率。
94 名患者被随机分配（索拉非尼-GEMOX：n=48；索拉非尼：n=46）。中位年龄为 64 岁，PS 0（69%）或 1（31%），63%的患者有肝硬化，29%的患者有门静脉血栓形成，70%的患者有肝外疾病。索拉非尼治疗的中位持续时间为 4 个月（1-51）；中位 GEMOX 周期数为 7（1-16）。索拉非尼-GEMOX 和索拉非尼组的 4 个月 PFS 率分别为 64%和 61%；中位 PFS 和 OS 分别为 6.2（95%CI：3.8-6.8）和 13.5（7.5-16.2）个月，4.6（3.9-6.2）和 14.8（12.2-22.2）个月。索拉非尼-GEMOX 和索拉非尼单独组的客观缓解率/疾病控制率分别为 9%/70%和 15%/77%。主要毒性反应为（索拉非尼-GEMOX/索拉非尼）中性粒细胞减少（23%/0）、血小板减少（33%/0）、腹泻（18%/9）、周围神经病（5%/0）和手足综合征（5%/18）。
添加 GEMOX 对 ORR 有影响，作为一线全身治疗耐受性良好。PFS 的获益似乎适中；没有计划进行后续研究。
