Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma.
BACKGROUND
Darinaparsin is a novel organic arsenic that reaches higher intracellular concentration with decreased toxicity compared to inorganic arsenic. We conducted a multi-center phase II study with darinaparsin in patients with advanced HCC.


METHODS
Eligibility criteria included unresectable or metastatic measurable HCC, up to two prior systemic treatments, ECOG performance status < or = 2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was administered at 420 mg/m(2) intravenously, twice weekly at least 72 h apart for 3 weeks in a 4-week cycle. The primary end point was response rate. A Simon two-stage design was used.


RESULTS
Among 15 patients in the first stage, no objective responses were observed. Two patients had stable disease. The median number of cycles on study per patient was 2 (1-6). The median progression free survival and overall survival were 55 days (95% confidence interval: 50-59) and 190 days (95% confidence interval: 93-227), respectively. No treatment related hospitalizations or deaths occurred. Treatment related grade 1-2 toxicities included nausea, vomiting (26.7% each), fatigue (20%), anorexia and diarrhea (13.3% each). Grade 3 anorexia, wheezing, agitation, abdominal pain and SGPT were observed in 1 patient each (6.7%). One patient experienced grade 4 hypoglycemia (6.7%).


CONCLUSIONS
Darinaparsin could be safely administered with tolerable toxicity profiles, and no QTc prolongation in patients with advanced HCC. However, at this dose and schedule, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis.
Wu
Jennifer
J
Department of Medical Oncology, NYU School of Medicine, New York, NY, USA. Jennifer.wu@nyumc.org
Henderson
Charles
C
Feun
Lynn
L
Van Veldhuizen
Peter
P
Gold
Philip
P
Zheng
Hui
H
Ryan
Theresa
T
Blaszkowsky
Lawrence S
LS
Chen
Haobin
H
Costa
Max
M
Rosenzweig
Barry
B
Nierodzik
MaryLynn
M
Hochster
Howard
H
Muggia
Franco
F
Abbadessa
Giovanni
G
Lewis
Jonathan
J
Zhu
Andrew X
AX
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001152:Arsenicals / Q000009:adverse effects / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005978:Glutathione / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001152:Arsenicals; C515055:darinaparsin; D005978:Glutathione