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Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

  • PHASE II STUDIES
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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.

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Authors and Affiliations

  1. Department of Medical Oncology, NYU School of Medicine, New York, NY, USA

    Jennifer Wu, Theresa Ryan, Howard Hochster & Franco Muggia

  2. Department of Medical Oncology, Piedmont Hospital Research Institute, Atlanta, GA, USA

    Charles Henderson

  3. Department of Medical Oncology, University of Miami Hospital and Clinics, Miami, FL, USA

    Lynn Feun

  4. Department of Hematology and Medical Oncology, Kansas City Veterans Administration Medical Center, Kansas, MO, USA

    Peter Van Veldhuizen

  5. Department of Medical Oncology, Swedish Cancer Institute Research, Seattle, WA, USA

    Philip Gold

  6. Research, Ziopharm Oncology Inc., Boston, MA, USA

    Giovanni Abbadessa & Jonathan Lewis

  7. Department of Biostatistics, Massachusetts General Hospital, Boston, MA, USA

    Hui Zheng

  8. Department of Medical Oncology, Massachusetts General Hospital, Boston, MA, USA

    Lawrence S. Blaszkowsky & Andrew X. Zhu

  9. Department of Environmental Medicine, NYU School of Medicine, New York, NY, USA

    HaoBin Chen & Max Costa

  10. Department of Cardiology, NYU School of Medicine, New York, NY, USA

    Barry Rosenzweig

  11. Department of Hematology and Medical Oncology, NYU School of Medicine, New York, NY, USA

    MaryLynn Nierodzik

  12. NYU Cancer Institute, BCD 556, Bellevue Hospital, 462 First Ave., New York, NY, 10016, USA

    Jennifer Wu

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  1. Jennifer Wu
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Correspondence to Jennifer Wu.

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Wu, J., Henderson, C., Feun, L. et al. Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. Invest New Drugs 28, 670–676 (2010). https://doi.org/10.1007/s10637-009-9286-9

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  • DOI: https://doi.org/10.1007/s10637-009-9286-9

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