Lind Pehr A, Naucler Gisela, Holm Agneta, Gubanski Michael, Svensson Christer
Department of Oncology, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Acta Oncol. 2007;46(2):230-3. doi: 10.1080/02841860600693473.
Presently, no effective systemic therapy is available for patients with advanced hepatocellular carcinoma (aHCC). We sought to determine whether systemic treatment with pegylated liposomal doxorubicin (PLD) would yield a response rate of 20% in chemotherapy naïve patients with aHCC. The study was designed according to the phase II Gehan two-step procedure with a precision of 10%. Enrollment criteria included histological diagnosis and radiological documentation of unresectable/metastatic HCC, WHO PS 0-2, relatively normal organ function, life expectancy greater than three months, lack of cardiomyopathy and active cardiac disease NYHA > or = II. PLD (40 mg/m(2) IV 1h-infusion) was administered on d1 q 4 wk and response to treatment was evaluated radiologically every 3rd cycle (WHO-criteria). Secondary endpoints included overall (OS) and progression free survival (PFS) and registration of toxicity. The median number of administered PLD cycles was 3. The best radiological response among the first 14 patients was 1 PR, 5 SD, 3 PD, and 6 NE due to progressive disease clinically (Step 1). The 15th patient did not respond to the PLD-therapy and the study was closed for accrual as the pre-planned analysis could be executed (Step 2). A response rate > or = 20% could be ruled out. The median PFS and OS survival was 82 days and 130 days, respectively. Adverse events were generally mild in the subgroup of patients without signs of moderate hepatic failure at base line. Patients with WHO PS 2, liver tumour involvement >50%, bilirubin > or = 34 micromol/L, albumin <33 g/L, and/or Child Pugh B were unlikely to survive >90 days. PLD can be delivered safely in patients with aHCC and no signs of moderate hepatic failure. The therapy resulted, however, in few responses or cases of disease stabilization and has thus very limited activity in aHCC. Future studies on systemic chemotherapy should focus on patients without moderate hepatic failure, with WHO PS <2, and with liver tumour involvement <50%.
目前，晚期肝细胞癌（aHCC）患者尚无有效的全身治疗方法。我们试图确定聚乙二醇化脂质体阿霉素（PLD）全身治疗初治的aHCC患者的缓解率是否能达到20%。该研究根据II期Gehan两步法设计，精度为10%。纳入标准包括不可切除/转移性HCC的组织学诊断和影像学记录、WHO体能状态0 - 2级、器官功能相对正常、预期寿命大于3个月、无心肌病且无NYHA>或=II级的活动性心脏疾病。PLD（40mg/m²静脉滴注1小时）于第1天每4周给药一次，每3个周期进行影像学评估治疗反应（WHO标准）。次要终点包括总生存期（OS）和无进展生存期（PFS）以及毒性记录。PLD给药周期的中位数为3。前14例患者中最佳的影像学反应为1例部分缓解（PR）、5例疾病稳定（SD）、3例疾病进展（PD），6例因临床疾病进展为疾病未评价（NE）（步骤1）。第15例患者对PLD治疗无反应，由于可进行预先计划的分析，研究停止入组（步骤2）。可以排除缓解率>或=20%的情况。PFS和OS的中位数分别为82天和130天。在基线时无中度肝衰竭迹象的患者亚组中，不良事件一般较轻。WHO体能状态2级、肝肿瘤累及>50%、胆红素>或=34微摩尔/升、白蛋白<33克/升和/或Child Pugh B级的患者存活超过90天的可能性不大。PLD可安全用于无中度肝衰竭迹象的aHCC患者。然而，该治疗导致的缓解或疾病稳定情况很少，因此在aHCC中的活性非常有限。未来关于全身化疗的研究应聚焦于无中度肝衰竭、WHO体能状态<2级且肝肿瘤累及<50%的患者。
