Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

Abstract

e15630 Background: Inorganic arsenic has reported activity in advanced hepatocellular carcinoma (HCC) in Asia, yet its efficacy is limited by liver toxicity. Darinaparsin is a novel organic arsenic that is capable of reaching higher intracellular concentration in cells with decreased toxicity compared to inorganic arsenic. It is highly active as a single agent in HCC cell lines and animal tumor models. 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 ≤2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was given at 420 mg/m2 intravenously administered over 60 minutes through a central line, twice weekly at least 72 hours apart for three weeks followed by one-week rest in a four-week cycle. The primary end point of the study was response rate. A Simon two-stage design was used to assess the efficacy of darinaparsin and the study would be terminated if no responses were observed after the first stage. Results: The planned 15 patients of the first stage were enrolled: median age = 60 (35 - 79). M/F = 14/1, ECOG performance status 0/1= 4/11, Child Pugh class A/B = 11/4. Seven patients received prior systemic chemotherapies. No objective responses were observed. Three 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. Treatment was well tolerated. No treatment related hospitalizations or deaths occurred. Treatment related grade 1–2 toxicities included nausea/vomiting (31%), fatigue (23%), anorexia (15%) and diarrhea (15%). Grade 3 anorexia, wheezing, agitation, right upper quadrant pain and SGPT were observed in 1 patient each (8%), 1 patient experienced grade 4 hypoglycemia (8%). Conclusions: Darinaparsin was safely administered with tolerable toxicity profiles in HCC patients. However, it has shown no objective responses in HCC and this trial was terminated as planned after the first stage of efficacy analysis. [Table: see text]