Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

Jennifer Wu, Charles Henderson, Lynn Feun, Peter Van Veldhuizen, Philip Gold, Hui Zheng, Theresa Ryan, Lawrence S. Blaszkowsky, Haobin Chen, Max Costa, Barry Rosenzweig, Marylynn Nierodzik, Howard Hochster, Franco Muggia, Giovanni Abbadessa, Jonathan Lewis, Andrew X. Zhu

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Summary: 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 ≤2, Child Pugh Class A or B and adequate organ functions. Darinaparsin was administered at 420 mg/m2 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.

Original languageEnglish (US)
Pages (from-to)670-676
Number of pages7
JournalInvestigational New Drugs
Volume28
Issue number5
DOIs
StatePublished - Oct 1 2010

Keywords

  • Clinical trials
  • Darinaparsin
  • Hepatocellular carcinoma
  • Phase II study

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

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    Wu, J., Henderson, C., Feun, L., Van Veldhuizen, P., Gold, P., Zheng, H., Ryan, T., Blaszkowsky, L. S., Chen, H., Costa, M., Rosenzweig, B., Nierodzik, M., Hochster, H., Muggia, F., Abbadessa, G., Lewis, J., & Zhu, A. X. (2010). Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. Investigational New Drugs, 28(5), 670-676. https://doi.org/10.1007/s10637-009-9286-9