Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea.
Hepatobiliary Pancreat Dis Int. 2019 Feb;18(1):62-66. doi: 10.1016/j.hbpd.2018.12.009. Epub 2018 Dec 28.
Sodium meta-arsenite (NaAsO, KML001) is a potential oral anticancer agent acting on telomerase and telomere length. This prospective study evaluated its safety, tolerability, and effectiveness as salvage chemotherapy in patients with advanced biliary tract cancer (BTC) resistant to gemcitabine-based chemotherapy.
Forty-four patients (21 women and 23 men) with advanced BTC and failure history of gemcitabine-based chemotherapy, performance status (PS) 0-2, normal cardiac, hepatic, and renal function were enrolled. Daily dose of KML001 (7.5 mg. p.o.) was administered to eligible subjects for 24 weeks divided into six treatment cycles. Response was evaluated bimonthly using CT.
After an average of 1.5 months of treatment (range: 0.5-10.0), 3 patients (6.8%) obtained progression-free status, 23 patients (52.3%) had disease progression, and 18 patients (40.9%) dropped out before evaluation. One patient (2.3%) completed six treatment cycles without progression. During the treatment, morphine dosage kept the same or decreased in 20 patients (47.6%). Nine patients (20.5%) experienced grade-3 adverse events (AEs), while no patient experienced grade-4 AEs. The most common AEs were liver enzyme elevation (11/44, 25%) and anemia (10/44, 22.7%). KML001 was discontinued in six patients (13.6%) due to AEs, including liver toxicity (n = 3), QTc prolongation (n = 2), and abdominal pain (n = 1).
KML001 did not have enough anticancer effect on patients with advanced BTC resistant to gemcitabine. However, KML001 was safe and well-tolerable in terms of AEs and pain control when used as salvage therapy. Further studies are needed to establish arsenic agents as a reliable treatment option in patients with BTC.
亚砷酸钠（NaAsO，KML001）是一种潜在的口服抗癌药物，作用于端粒酶和端粒长度。本前瞻性研究评估了其在对吉西他滨为基础的化疗耐药的晚期胆道癌（BTC）患者中的安全性、耐受性和有效性作为挽救化疗。
44 名晚期 BTC 且有吉西他滨为基础的化疗失败史、表现状态（PS）0-2、正常心脏、肝、肾功能的患者入组。符合条件的患者每日口服 KML001（7.5mg，po），24 周分为 6 个治疗周期。每两个月使用 CT 评估一次反应。
在平均 1.5 个月的治疗后（范围：0.5-10.0），3 名患者（6.8%）获得无进展状态，23 名患者（52.3%）疾病进展，18 名患者（40.9%）在评估前退出。1 名患者（2.3%）完成了 6 个治疗周期而无进展。在治疗过程中，20 名患者（47.6%）的吗啡剂量保持不变或减少。9 名患者（20.5%）发生 3 级不良事件（AE），无 4 级 AE。最常见的 AE 是肝酶升高（11/44，25%）和贫血（10/44，22.7%）。由于 AE，6 名患者（13.6%）停用 KML001，包括肝毒性（n=3）、QTc 延长（n=2）和腹痛（n=1）。
KML001 对吉西他滨耐药的晚期 BTC 患者的抗癌作用不足。然而，KML001 作为挽救治疗时，在 AE 和疼痛控制方面是安全且耐受良好的。需要进一步的研究来确立砷剂作为 BTC 患者可靠的治疗选择。
