Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma

Evan Glazer, Mauro Piccirillo, Vittorio Albino, Raimondo Di Giacomo, Raffaele Palaia, Angelo A. Mastro, Gerardo Beneduce, Giuseppe Castello, Vincenzo De Rosa, Antonella Petrillo, Paolo A. Ascierto, Steven A. Curley, Francesco Izzo

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Purpose: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, α-fetoprotein (AFP) levels, and serum arginine levels. Patients and Methods: Eighty patients were randomly assigned to receive either 80 IU/m2 or 160 IU/m2 of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. Results: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (±SE) survival for all subjects was 15.8 months (474 days ± 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. Conclusion: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

Original languageEnglish (US)
Pages (from-to)2220-2226
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number13
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

Hepatocellular Carcinoma
Arginine
Citrullinemia
Fetal Proteins
Survival Analysis
Random Allocation
ADI PEG20
Serum
Reaction Time
Antibody Formation
Survival Rate
Survival
arginine deiminase
Antibodies
Therapeutics
Pharmaceutical Preparations
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma. / Glazer, Evan; Piccirillo, Mauro; Albino, Vittorio; Di Giacomo, Raimondo; Palaia, Raffaele; Mastro, Angelo A.; Beneduce, Gerardo; Castello, Giuseppe; De Rosa, Vincenzo; Petrillo, Antonella; Ascierto, Paolo A.; Curley, Steven A.; Izzo, Francesco.

In: Journal of Clinical Oncology, Vol. 28, No. 13, 01.05.2010, p. 2220-2226.

Research output: Contribution to journalArticle

Glazer, E, Piccirillo, M, Albino, V, Di Giacomo, R, Palaia, R, Mastro, AA, Beneduce, G, Castello, G, De Rosa, V, Petrillo, A, Ascierto, PA, Curley, SA & Izzo, F 2010, 'Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma', Journal of Clinical Oncology, vol. 28, no. 13, pp. 2220-2226. https://doi.org/10.1200/JCO.2009.26.7765
Glazer, Evan ; Piccirillo, Mauro ; Albino, Vittorio ; Di Giacomo, Raimondo ; Palaia, Raffaele ; Mastro, Angelo A. ; Beneduce, Gerardo ; Castello, Giuseppe ; De Rosa, Vincenzo ; Petrillo, Antonella ; Ascierto, Paolo A. ; Curley, Steven A. ; Izzo, Francesco. / Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 13. pp. 2220-2226.
@article{2761f551293940daa0ac51c6dda8b985,
title = "Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma",
abstract = "Purpose: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, α-fetoprotein (AFP) levels, and serum arginine levels. Patients and Methods: Eighty patients were randomly assigned to receive either 80 IU/m2 or 160 IU/m2 of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. Results: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (±SE) survival for all subjects was 15.8 months (474 days ± 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. Conclusion: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.",
author = "Evan Glazer and Mauro Piccirillo and Vittorio Albino and {Di Giacomo}, Raimondo and Raffaele Palaia and Mastro, {Angelo A.} and Gerardo Beneduce and Giuseppe Castello and {De Rosa}, Vincenzo and Antonella Petrillo and Ascierto, {Paolo A.} and Curley, {Steven A.} and Francesco Izzo",
year = "2010",
month = "5",
day = "1",
doi = "10.1200/JCO.2009.26.7765",
language = "English (US)",
volume = "28",
pages = "2220--2226",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "13",

}

TY - JOUR

T1 - Phase II Study of Pegylated Arginine Deiminase for Nonresectable and Metastatic Hepatocellular Carcinoma

AU - Glazer, Evan

AU - Piccirillo, Mauro

AU - Albino, Vittorio

AU - Di Giacomo, Raimondo

AU - Palaia, Raffaele

AU - Mastro, Angelo A.

AU - Beneduce, Gerardo

AU - Castello, Giuseppe

AU - De Rosa, Vincenzo

AU - Petrillo, Antonella

AU - Ascierto, Paolo A.

AU - Curley, Steven A.

AU - Izzo, Francesco

PY - 2010/5/1

Y1 - 2010/5/1

N2 - Purpose: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, α-fetoprotein (AFP) levels, and serum arginine levels. Patients and Methods: Eighty patients were randomly assigned to receive either 80 IU/m2 or 160 IU/m2 of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. Results: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (±SE) survival for all subjects was 15.8 months (474 days ± 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. Conclusion: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

AB - Purpose: It is well known that hepatocellular carcinoma (HCC) is an arginine auxotroph due to argininosuccinate synthetase I deficiency. This study's purpose was to evaluate the effects of pegylated arginine deiminase (ADI) in terms of toxicity, tumor response, α-fetoprotein (AFP) levels, and serum arginine levels. Patients and Methods: Eighty patients were randomly assigned to receive either 80 IU/m2 or 160 IU/m2 of ADI weekly for up to 6 months. Adverse events, serum arginine, AFP levels, and antibody production against ADI were measured on a regular basis. In addition, disease response and time to progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) and survival rates were evaluated. Results: Four patients were excluded from the survival analysis because they developed exclusion criteria after randomization, but before first treatment. The number of patients in the two cohorts were similar (n = 37 in the low-dose cohort, n = 39 in the high-dose cohort). Mean (±SE) survival for all subjects was 15.8 months (474 days ± 39 days) from time of diagnosis of unresectable disease. Arginine levels remained below baseline for 50 days while antibodies against ADI reached a plateau at approximately the same time. There were no deaths attributed to ADI treatment. Only two patients were withdrawn for immunogenic-related adverse events. Grade 2, 3, or 4 toxicities were recorded in 92, 19, and 0 patients, respectively. Conclusion: Pegylated ADI is a promising drug that capitalizes on a significant enzymatic deficiency in HCC. It is safe, well tolerated, and may benefit patients with unresectable HCC.

UR - http://www.scopus.com/inward/record.url?scp=77952316981&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952316981&partnerID=8YFLogxK

U2 - 10.1200/JCO.2009.26.7765

DO - 10.1200/JCO.2009.26.7765

M3 - Article

VL - 28

SP - 2220

EP - 2226

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 13

ER -