PMID- 30612929
OWN - NLM
STAT- MEDLINE
DCOM- 20190529
LR  - 20221207
IS  - 1499-3872 (Print)
VI  - 18
IP  - 1
DP  - 2019 Feb
TI  - KML001, an arsenic compound, as salvage chemotherapy in refractory biliary tract 
      cancers: A prospective study.
PG  - 62-66
LID - S1499-3872(18)30275-3 [pii]
LID - 10.1016/j.hbpd.2018.12.009 [doi]
AB  - 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 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. 
      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.
CI  - Copyright (c) 2018. Published by Elsevier B.V.
FAU - Jo, Jung Hyun
AU  - Jo JH
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Kang, Huapyong
AU  - Kang H
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Lee, Hee Seung
AU  - Lee HS
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Chung, Moon Jae
AU  - Chung MJ
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Park, Jeong Youp
AU  - Park JY
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Bang, Seungmin
AU  - Bang S
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Park, Seung Woo
AU  - Park SW
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea.
FAU - Song, Si Young
AU  - Song SY
AD  - Division of Gastroenterology, Department of Internal Medicine, Severance 
      Hospital, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, 
      Seoul 120-752, Korea. Electronic address: sysong@yuhs.ac.
LA  - eng
PT  - Journal Article
DEP - 20181228
PL  - Singapore
TA  - Hepatobiliary Pancreat Dis Int
JT  - Hepatobiliary & pancreatic diseases international : HBPD INT
JID - 101151457
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Arsenites)
RN  - 0 (Sodium Compounds)
RN  - 0W860991D6 (Deoxycytidine)
RN  - 48OVY2OC72 (sodium arsenite)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Administration, Oral
MH  - Aged
MH  - Antineoplastic Agents/*administration & dosage/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use
MH  - Arsenites/*administration & dosage/adverse effects
MH  - Biliary Tract Neoplasms/diagnostic imaging/*drug therapy/mortality/pathology
MH  - Deoxycytidine/administration & dosage/analogs & derivatives
MH  - Drug Administration Schedule
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Progression-Free Survival
MH  - Prospective Studies
MH  - *Salvage Therapy
MH  - Sodium Compounds/*administration & dosage/adverse effects
MH  - Time Factors
MH  - Tomography, X-Ray Computed
MH  - Gemcitabine
OTO - NOTNLM
OT  - Biliary tract neoplasms
OT  - Cholangiocarcinoma
OT  - Gallbladder neoplasms
OT  - KML001
OT  - Sodium meta-arsenite
EDAT- 2019/01/08 06:00
MHDA- 2019/05/30 06:00
CRDT- 2019/01/08 06:00
PHST- 2018/09/11 00:00 [received]
PHST- 2018/12/19 00:00 [accepted]
PHST- 2019/01/08 06:00 [pubmed]
PHST- 2019/05/30 06:00 [medline]
PHST- 2019/01/08 06:00 [entrez]
AID - S1499-3872(18)30275-3 [pii]
AID - 10.1016/j.hbpd.2018.12.009 [doi]
PST - ppublish
SO  - Hepatobiliary Pancreat Dis Int. 2019 Feb;18(1):62-66. doi: 
      10.1016/j.hbpd.2018.12.009. Epub 2018 Dec 28.