studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 423A
vious hepatic decompensation, and was also independent risk
factor for recurrence after curative therapy [HR (95% CI): 1.84
(1.25-2.72), p = 0.002] among 117 patients who received
curative therapy. The overall survival, decompensation-free
survival, and recurrence-free survival was better in entecavir
treated patients than lamivudine treated patients . The survival
benefit of choosing high potent drug over less potent drug will
be higher when patient survival is long enough. Low-potent
drug may be a valuable option for those with low expected
survival, especially in resource-limited setting, but high-potent
drug should be the preferred choice in the rest of HBV-related
HCC patients.
Disclosures:
The following authors have nothing to disclose: jung hee kim, Dong Hyun Sinn,
Kyunga Kim, Geum-Youn Gwak, Yong-Han Paik, Moon Seok Choi, Joon Hyeok
Lee, Kwang Cheol Koh, Seung Woon Paik
423
Long term outcome after resection of intermediate
hepatocellular carcinoma: comparison to transarterial
chemoembolization
DAEGEON AHN, Dong Hyun Sinn, Geum-Youn Gwak, Moon
Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh, Seung Woon
Paik, Byung Chul Yoo; Gastroenterology, Samsung Medical Center,
Seoul, Korea (the Republic of)
Background and Aims: Transarterial chemoembolization
(TACE) is the first-line recommended therapy for patients with
intermediate hepatocellular carcinoma (HCC) in the BCLC staging
system. However, in clinical practice, some patients receive
hepatectomy. We compared long-term outcome in these
patients. Methods: A total of 277 patients with intermediate
stage HCC who were treated with either hepatectomy or TACE
were analyzed. Results: The median survival was significantly
better for resection than TACE (5.3 vs. 2.6 years, p = 0.002),
however, when adjusted for age, Child-Pugh Class, maximal
tumor size, tumor number, uni- or bi-lobal involvement, and AFP
levels, there was no significant survival difference by treatment
modality [Hazard ratio (HR): 1.42, 95% CI (0.91-2.22), p =
0.11]. In sub-group analysis, resection showed better survival
than TACE in Child-Pugh score 5, maximal tumor size ≤ 5cm
or > 10cm, and tumor number ≤ 3, however, there was no
survival difference in patients with Child-Pugh score ≥ 6, tumor
size between 5-10cm, and tumor number ≥ 4. When patients
were sub-grouped according to the Child-Pugh Class, tumor
number and size, resection (n = 26) provided survival benefit
over TACE (n = 58) for those with Child-Pugh class 5, less than
3 tumors, and tumor size ≤ 5cm or > 10cm [adjusted HR: 0.41
(95% CI: 0.20-0.84), p = 0.015], but not the rest of patients
[adjusted HR for resection (n = 26) vs. TACE (n = 167): 0.73
(95% CI: 0.44-1.21), p = 0.22]. Conclusion: Resection can
be first-line treatment option for intermediate stage HCC when
certain criteria are met. In this study, child-Pugh score 5, tumor
number ≤ 3, and tumor size ≤ 5 or > 10 cm were the criteria.
Disclosures:
The following authors have nothing to disclose: DAEGEON AHN, Dong Hyun
Sinn, Geum-Youn Gwak, Moon Seok Choi, Joon Hyeok Lee, Kwang Cheol Koh,
Seung Woon Paik, Byung Chul Yoo
424
TBI 302: A first-in-class therapy for the treatment of
advanced stage liver cancer
Steve Brookes 1 , Gary Levy 1,2 , Jin Seog Seo 1 , Murray J. Cutler 1 ,
Yvonne Frater 1 , Gord Adamson 1 , David Bell 1 ; 1 Drug Development,
Therapure Biopharma Inc., Mississauga, ON, Canada; 2 Multi
Orgon Transplant Program, University of Toronto Transplant Institute,
Toronto, ON, Canada
Hepatocellular carcinoma (HCC) is the second most common
cause of death from cancer worldwide; few treatment options
are available, especially for advanced stage disease. Current
standard of care provides only a modest improvement in overall
survival and is associated with poor quality of life. Therapure
has developed a novel drug delivery platform based upon
the attachment of therapeutic drugs to hemoglobin (Hb) as a
means of targeting the liver. TBI 302 is a hemoglobin-drug conjugate
(HDC) designed to deliver the anticancer drug floxuridine
(FUdR) to the liver to improve the effectiveness of treatment
for HCC. Systemic toxicity associated with free FUdR restricts its
use to locoregional administration (0.2-0.5 mg/kg/d) via continuous
hepatic arterial infusion (HAI). Although HAI of FUdR
can reduce hepatic tumor burden, toxicity from HAI FUdR and
complications associated with direct hepatic infusion pumps
can be significant. HDC technology uses Hb as an innovative
drug carrier that exploits the natural pathway for hemoglobin
clearance predominantly through the liver to provide selective
drug targeting while preserving FUdR activity following standard
intravenous (IV) infusion. To establish a safe starting dose
for a first-in-human Phase 1 trial, a GLP-compliant repeat dose
preclinical safety study of TBI 302 in cynomolgus monkeys was
conducted. TBI 302 administered by 1-hour IV infusion once
per week for 8 weeks at doses of 2, 5, and 10.5 mg/kg (0.08,
0.19, and 0.4 mg/kg FUdR, respectively) was well tolerated
at all dose levels. Increasing doses of TBI 302 resulted in proportional
increases in area under the concentration-time curve
(AUC) and maximum concentration (Cmax) of total plasma
FUdR. No clinical signs or biochemical toxicity was associated
with IV infusion of TBI 302. The no-observed-adverse-effect
level (NOAEL) of TBI 302 was determined to be the highest
dose level of 10.5 mg/kg (0.4 mg/kg FUdR). TBI 302 is projected
to have a half-life of approximately 5 hours in humans. A
Phase I safety study of TBI 302 as second-line therapy in HCC
has been approved by the US FDA. The primary objective is
to determine safety and tolerability of TBI 302. The secondary
objectives are to determine TBI 302 pharmacokinetics and
effects on tumor burden. Therapure’s HDC platform represents
a new class of therapy that offers liver-specific targeting for
a wide range of hepatic diseases, while potentially reducing
extra-hepatic toxicity of drugs.
Disclosures:
Jin Seog Seo - Employment: Therapure Biopharma Inc
Murray J. Cutler - Employment: Therapure Biopharma
Yvonne Frater - Management Position: Therapure
Gord Adamson - Employment: Therapure Biopharma Inc.
David Bell - Employment: Therapure Biopharma Inc.
The following authors have nothing to disclose: Steve Brookes, Gary Levy