Ogasawara Sadahisa, Chiba Tetsuhiro, Ooka Yoshihiko, Kanogawa Naoya, Motoyama Tenyu, Suzuki Eiichiro, Tawada Akinobu, Kanai Fumihiko, Yokosuka And Osamu
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
Invest New Drugs. 2014 Aug;32(4):762-8. doi: 10.1007/s10637-014-0097-2. Epub 2014 Apr 16.
Several pilot studies have demonstrated the effectiveness of combination therapy with pyrimidine fluoride and interferon for advanced hepatocellular carcinoma.This study aimed to determine the recommended dose of capecitabine combined with peginterferon α-2a (Phase I) and evaluate its safety and efficacy for sorafenib-refractory advanced hepatocellular carcinoma (Phase II).
Capecitabine was administered daily on days 1-14, while peginterferon α-2a was administered on days 1, 8, and 15. The cycle was repeated every 21 days. The patients were scheduled to receive capecitabine [mg/(m(2)∙day)] and peginterferon α-2a (μg/week) at 3 dose levels in phase I: 1200 and 90 (level 1), 1600 and 90 (level 2), and 2000 and 90 (level 3), respectively.
A total of 30 patients were enrolled. The recommended dose was level 3. Among the 24 patients receiving the drug at the recommended dosage, 2 (8 %) exhibited a partial response, 9 (38 %) exhibited stable disease, 10 (42 %) exhibited progressive disease, and 3 (13 %) were not evaluated. The median time to progression and overall survival were 3.0 months and 7.2 months, respectively. The most common toxicities were decreased white blood cell (88 %), neutrophil (88 %), and platelet counts (58 %); fatigue (50 %); and palmar-plantar erythrodysesthesia syndrome (42 %). Four patients (17 %) discontinued treatment because of severe adverse events.
Capecitabine at 2000 mg/(m(2)∙day) combined with peginterferon α-2a (90 μg/week) exhibited moderate, albeit manageable, toxicity and was declared as the recommended phase II dose. Further research is required to refine the efficacy of this combination.
多项试点研究已证明氟尿嘧啶与干扰素联合治疗晚期肝细胞癌的有效性。本研究旨在确定卡培他滨联合聚乙二醇干扰素α-2a的推荐剂量（I期），并评估其对索拉非尼耐药的晚期肝细胞癌的安全性和疗效（II期）。
卡培他滨在第1 - 14天每日给药，聚乙二醇干扰素α-2a在第1、8和15天给药。每21天重复一个周期。在I期，患者按3个剂量水平接受卡培他滨[mg/(m²·天)]和聚乙二醇干扰素α-2a（μg/周）：分别为1200和90（1级）、1600和90（2级）、2000和90（3级）。
共纳入30例患者。推荐剂量为3级。在24例按推荐剂量接受药物治疗的患者中，2例（8%）出现部分缓解，9例（38%）病情稳定，10例（42%）病情进展，3例（13%）未评估。中位疾病进展时间和总生存期分别为3.0个月和7.2个月。最常见的毒性反应为白细胞减少（占88%）、中性粒细胞减少（占88%）、血小板计数减少（占58%）；疲劳（占50%）；以及手足红斑感觉异常综合征（占42%）。4例患者（17%）因严重不良事件停止治疗。
卡培他滨2000 mg/(m²·天)联合聚乙二醇干扰素α-2a（90 μg/周）显示出中度毒性，尽管可控制，被宣布为推荐的II期剂量。需要进一步研究以提高这种联合治疗的疗效。
