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Pegylated Arginine Deiminase Treatment of Patients With Unresectable Hepatocellular Carcinoma: Results From Phase I/II Studies
Abstract
Purpose: Recently, we reported that a large number of human hepatocellular cancer (HCC) cell lines were auxotrophic for arginine. Here we report the results obtained with the amino acid–degrading enzyme arginine deiminase (ADI) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) as a means of lowering plasma arginine to treat HCC. The study was a cohort dose-escalation phase I/II study. Patients and Methods: Pharmacodynamic studies indicated an ADI-SS PEG 20,000 mw dose level of 160 U/m 2 was sufficient to lower plasma arginine from a resting level of approximately 130 μmol/L to below the level of detection (< 2 μmol/L) for more than 7 days, a dose later defined as the optimal biologic dose. All patients were to receive three cycles at the optimum biologic dose. Results: This therapy was well tolerated, even in patients who had no detectable plasma arginine for 3 continuous months of therapy. Of the 19 patients enrolled, two had a complete response, seven had a partial response, seven had stable disease, and three had progressive disease. The median survival for the 19 patients enrolled on this study was 410 days, with four patients still alive at present (> 680 days). Conclusion: Elimination of all detectable plasma arginine in patients with HCC was well tolerated and seemed to be effective in the treatment of some patients with HCC. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with HCC as well as other human tumors auxotrophic for arginine is warranted.
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“Recombinant pegylated arginine deiminase (ADI-PEG20) has been tested in clinical trials to treat melanoma and hepatocellular carcinoma with some therapeutic benefit (Ascierto et al., 2005; Izzo et al., 2004; Ott et al., 2013; Szlosarek et al., 2013; Yang et al., 2010).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Izzo et al., 2004
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Metadata
- Authors
- Izzo, F., Marra, P., Beneduce, G., Castello, G., Vallone, P., De Rosa, V., Cremona, F., Ensor, C. M., Holtsberg, F. W., Bomalaski, J. S., Clark, M. A., Ng, C., & Curley, S. A.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- From the Pascale National Cancer Institute, Naples, Italy; Phoenix Pharmacologics Inc, and University of Kentucky, Lexington, KY; and M.D. Anderson Cancer Center, University of Texas, Houston, TX.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2004-05-15
- Volume
- 22
- Issue
- 10
- Pages
- 1815-1822
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2168974457
- Cited by
- 250
- References
- 42
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 11 · 2022: 9 · 2021: 14 · 2020: 10 · 2019: 7 · 2018: 16 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 14 · 2013: 15 · 2012: 15
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- arginine deiminase, pegylated arginine deiminase, hepatocellular carcinoma, arginine auxotrophy, dose escalation, pharmacodynamics, tumor response, survival
- MeSH terms
- Adult, Aged, Drug Administration Schedule, Female, Carcinoma, Hepatocellular, Humans, Hydrolases, Injections, Intramuscular, Liver Neoplasms, Male, Middle Aged, Polyethylene Glycols, Tomography, X-Ray Computed, Cohort Studies, Survival Analysis, Treatment Outcome, Disease-Free Survival
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