The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
Pegylated Arginine Deiminase Treatment of Patients With Metastatic Melanoma: Results From Phase I and II Studies
Abstract
Purpose: Individuals with metastatic melanoma have a poor prognosis. Many human melanomas are auxotrophic for arginine, and arginine is not an essential amino acid in humans. We hypothesized that this auxotrophy may be therapeutically exploited. A novel amino acid–degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma. Patients and Methods: Two cohort dose-escalation studies were performed. A phase I study in the United States enrolled 15 patients, and a phase I to II study in Italy enrolled 24 patients. The Italian patients also received two subsequent cycles of treatment, each consisting of four once-weekly injections of 160 U/m 2. The goals of these studies were to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and the antitumor activity of ADI-SS PEG 20,000 mw. Results: PK and PD studies indicated that a dose of 160 U/m 2 lowered plasma arginine from a resting level of approximately 130 μmol/L to less than 2 μmol/L for at least 7 days; nitric oxide levels also were lowered. There were no grade 3 or 4 toxicities directly attributable to the drug. Six of 24 phase I to II patients responded to treatment (five partial responses and one complete response; 25% response rate) and also had prolonged survival. Conclusion: Elimination of all detectable plasma arginine in patients with metastatic melanoma was well tolerated and may be effective in the treatment of this cancer. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with metastatic melanoma 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 Ascierto et al., 2005
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iNOS-mediated nitric oxide production and its regulation
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Tsao, H., Atkins, M. B., & Sober, A. J. (2004) · New England Journal of Medicine · doi:10.1056/nejmra041245 · Cited by 869
Histone Deimination Antagonizes Arginine Methylation
Cuthbert, G. L., Daujat, S., Snowden, A. W., Erdjument‐Bromage, H., Hagiwara, T., Yamada, M., Schneider, R., Gregory, P. D., Tempst, P., Bannister, A. J., et al. (2004) · Cell · doi:10.1016/j.cell.2004.08.020 · Cited by 840
Global perspectives of contemporary epidemiological trends of cutaneous malignant melanoma
Lens, M. B., & Dawes, M. G. (2004) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2004.05708.x · Cited by 566
Kirkwood, J. M., Manola, J. B., Ibrahim, J. G., Sondak, V. K., Ernstoff, M. S., & Rao, U. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-1103-3 · Cited by 550
Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years?
Eggermont, A. M. M., & Kirkwood, J. M. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.04.030 · Cited by 384
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Regulation of Nitric Oxide Production by Arginine Metabolic Enzymes
Mori, M., & Gotoh, T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3169 · Cited by 359
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Metadata
- Authors
- Ascierto, P. A., Scala, S., Castello, G., Daponte, A., Simeone, E., Ottaiano, A., Beneduce, G., De Rosa, V., Izzo, F., Melucci, M. T., Ensor, C. M., Prestayko, A. W., Holtsberg, F. W., Bomalaski, J. S., Clark, M. A., Savaraj, N., Feun, L. G., & Logan, T. F.
- Affiliations
- University of Kentucky (US)
- From the Pascale National Cancer Institute, Naples, Italy; Phoenix Pharmacologics, Inc; University of Kentucky, Lexington, KY; Hematology and Oncology Division, University of Miami; Miami Veterans Affairs Medical Center, Miami, FL; and Hematology and Oncology Division, Indiana University, Indianapolis, IN.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2005-10-20
- Volume
- 23
- Issue
- 30
- Pages
- 7660-7668
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2167874373
- Cited by
- 238
- References
- 53
- Citations by year
- 2025: 8 · 2024: 7 · 2023: 10 · 2022: 10 · 2021: 13 · 2020: 17 · 2019: 8 · 2018: 10 · 2017: 13 · 2016: 15 · 2015: 16 · 2014: 15 · 2013: 14 · 2012: 19
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Bacterial Cancer Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- metastatic melanoma, arginine deiminase, pegylated arginine deiminase, arginine auxotrophy, nitric oxide, enzyme conjugation, pharmacokinetics, pharmacodynamics, anticancer activity, dose escalation, safety and tolerability
- MeSH terms
- Adult, Aged, Aged, 80 and over, Arginine, Female, Humans, Hydrolases, Italy, Male, Melanoma, Middle Aged, Nitric Oxide, Polyethylene Glycols, Skin Neoplasms, United States, Survival Rate, Treatment Outcome, Maximum Tolerated Dose
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