Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

Jennifer Wu, Charles Henderson, Lynn G 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

27 Citations (Scopus)

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

Fingerprint

Hepatocellular Carcinoma
Anorexia
Arsenic
Confidence Intervals
Respiratory Sounds
darinaparsin
Alanine Transaminase
Hypoglycemia
Nausea
Abdominal Pain
Disease-Free Survival
Vomiting
Fatigue
Diarrhea
Appointments and Schedules
Hospitalization
Therapeutics
Survival

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

Wu, J., Henderson, C., Feun, L. G., Van Veldhuizen, P., Gold, P., Zheng, H., ... 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

Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. / Wu, Jennifer; Henderson, Charles; Feun, Lynn G; Van Veldhuizen, Peter; Gold, Philip; Zheng, Hui; Ryan, Theresa; Blaszkowsky, Lawrence S.; Chen, Haobin; Costa, Max; Rosenzweig, Barry; Nierodzik, Marylynn; Hochster, Howard; Muggia, Franco; Abbadessa, Giovanni; Lewis, Jonathan; Zhu, Andrew X.

In: Investigational New Drugs, Vol. 28, No. 5, 01.10.2010, p. 670-676.

Research output: Contribution to journalArticle

Wu, J, Henderson, C, Feun, LG, Van Veldhuizen, P, Gold, P, Zheng, H, Ryan, T, Blaszkowsky, LS, Chen, H, Costa, M, Rosenzweig, B, Nierodzik, M, Hochster, H, Muggia, F, Abbadessa, G, Lewis, J & Zhu, AX 2010, 'Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma', Investigational New Drugs, vol. 28, no. 5, pp. 670-676. https://doi.org/10.1007/s10637-009-9286-9
Wu, Jennifer ; Henderson, Charles ; Feun, Lynn G ; Van Veldhuizen, Peter ; Gold, Philip ; Zheng, Hui ; Ryan, Theresa ; Blaszkowsky, Lawrence S. ; Chen, Haobin ; Costa, Max ; Rosenzweig, Barry ; Nierodzik, Marylynn ; Hochster, Howard ; Muggia, Franco ; Abbadessa, Giovanni ; Lewis, Jonathan ; Zhu, Andrew X. / Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma. In: Investigational New Drugs. 2010 ; Vol. 28, No. 5. pp. 670-676.
@article{c1431b474ee242d0947a40d053cb9578,
title = "Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma",
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.",
keywords = "Clinical trials, Darinaparsin, Hepatocellular carcinoma, Phase II study",
author = "Jennifer Wu and Charles Henderson and Feun, {Lynn G} and {Van Veldhuizen}, Peter and Philip Gold and Hui Zheng and Theresa Ryan and Blaszkowsky, {Lawrence S.} and Haobin Chen and Max Costa and Barry Rosenzweig and Marylynn Nierodzik and Howard Hochster and Franco Muggia and Giovanni Abbadessa and Jonathan Lewis and Zhu, {Andrew X.}",
year = "2010",
month = "10",
day = "1",
doi = "10.1007/s10637-009-9286-9",
language = "English",
volume = "28",
pages = "670--676",
journal = "Investigational New Drugs",
issn = "0167-6997",
publisher = "Kluwer Academic Publishers",
number = "5",

}

TY - JOUR

T1 - Phase II study of darinaparsin in patients with advanced hepatocellular carcinoma

AU - Wu, Jennifer

AU - Henderson, Charles

AU - Feun, Lynn G

AU - Van Veldhuizen, Peter

AU - Gold, Philip

AU - Zheng, Hui

AU - Ryan, Theresa

AU - Blaszkowsky, Lawrence S.

AU - Chen, Haobin

AU - Costa, Max

AU - Rosenzweig, Barry

AU - Nierodzik, Marylynn

AU - Hochster, Howard

AU - Muggia, Franco

AU - Abbadessa, Giovanni

AU - Lewis, Jonathan

AU - Zhu, Andrew X.

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

KW - Clinical trials

KW - Darinaparsin

KW - Hepatocellular carcinoma

KW - Phase II study

UR - http://www.scopus.com/inward/record.url?scp=77956060553&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77956060553&partnerID=8YFLogxK

U2 - 10.1007/s10637-009-9286-9

DO - 10.1007/s10637-009-9286-9

M3 - Article

VL - 28

SP - 670

EP - 676

JO - Investigational New Drugs

JF - Investigational New Drugs

SN - 0167-6997

IS - 5

ER -