KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study
Jung Hyun Jo, Huapyong Kang, Hee Seung Lee, Moon Jae Chung, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Si Young Song ∗
Division of Gastroenterology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Korea
Abstract：Background: Sodium meta-arsenite (NaAsO 2 , 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.
Methods: 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 func- tion 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.
Results: 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).
Conclusions: 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.
. [J]. Hepatobiliary Pancreat Dis Int, 2019, 18(1): 62-66.
Jo JH, Kang H, Lee HS, Chung MJ, Park JY, Bang S, Park SW, Song SY. KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract cancers: A prospective study. Hepatobiliary Pancreat Dis Int, 2019, 18(1): 62-66.
2019, Vol. 18 
