Gastroenterology Department, Pisa University Hospital, Via Paradisa 2, 56124 Pisa, Italy.
Expert Rev Anticancer Ther. 2012 Jul;12(7):869-75. doi: 10.1586/era.12.58.
Prospective randomized trials have proven that sorafenib is a valid treatment option for patients with advanced-stage hepatocellular carcinoma (HCC). The aim of the present study is to evaluate the effectiveness and safety of sorafenib in patients encountered in routine clinical practice.
From September 2008 to March 2011, 42 cirrhotic patients (30 male; 12 female; mean age: 70.2 ± 7.6 years; range: 56-85 years) with HCC of Barcelona Clinic Liver Cancer stage B (n = 5) or C (n = 37; mean size: 66.6 ± 42.3 mm; mean number per patient: 3.3 ± 2.8) were treated with sorafenib at either a standard dose of 800 mg/day (n = 29; 69.1%) or at 400 mg/day with subsequent dose escalation (ramp-up strategy; n = 13, 30.9%). Baseline clinical parameters were comparable. Clinical data and side effects, laboratory analyses (in particular, serum α-fetoprotein) and radiological data (tumor response according to amended RECIST criteria) were assessed every 3 months. Survival was calculated by Kaplan-Meier analysis.
Mean follow-up was 12.2 ± 9 months (range: 1-32 months). Median overall survival was 26.1 months with overall 6- and 12-month survival rates of 92.1 and 85%, respectively. Median time to radiological progression was 8 months. The progression-free rate was 64.3%. Fatigue, skin disorders and diarrhea were the most frequent grade 3-4 side effects. Treatment discontinuation occurred in 25 patients. The starting dose for the last 13 enrolled patients was 400 mg/day; in the absence of toxicity this dosage was gradually increased to 800 mg/day after 3 weeks ('ramp-up strategy'). No grade 3/4 adverse events were observed in the ramp-up group.
Sorafenib is a valid treatment option for advanced-stage HCC. Starting at a lower dosage may allow prolonged compliance to treatment and might be considered according to patient tolerance.
前瞻性随机试验已经证实，索拉非尼是晚期肝细胞癌（HCC）患者的有效治疗选择。本研究的目的是评估索拉非尼在常规临床实践中遇到的患者中的有效性和安全性。
从 2008 年 9 月至 2011 年 3 月，42 例肝硬化患者（30 名男性；12 名女性；平均年龄：70.2±7.6 岁；范围：56-85 岁）患有巴塞罗那临床肝癌分期 B（n=5）或 C（n=37；平均大小：66.6±42.3mm；平均每人 3.3±2.8 个）的 HCC 接受索拉非尼治疗，标准剂量 800mg/天（n=29；69.1%）或 400mg/天（n=13；30.9%），随后增加剂量。基线临床参数具有可比性。每 3 个月评估临床数据和副作用、实验室分析（特别是血清甲胎蛋白）和影像学数据（根据改良 RECIST 标准评估肿瘤反应）。通过 Kaplan-Meier 分析计算生存。
平均随访时间为 12.2±9 个月（范围：1-32 个月）。中位总生存期为 26.1 个月，总 6 个月和 12 个月生存率分别为 92.1%和 85%。中位影像学进展时间为 8 个月。无进展生存率为 64.3%。疲劳、皮肤疾病和腹泻是最常见的 3-4 级副作用。25 名患者停止治疗。最后 13 名入组患者的起始剂量为 400mg/天；在没有毒性的情况下，该剂量在 3 周后逐渐增加至 800mg/天（“爬坡策略”）。爬坡组未观察到 3/4 级不良事件。
索拉非尼是晚期 HCC 的有效治疗选择。起始剂量较低可能会延长治疗的依从性，并可根据患者的耐受性考虑。
