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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
Citations
Cites
Optimal two-stage designs for phase II clinical trials.
Simon, R. (1989) · Controlled Clinical Trials · doi:10.1016/0197-2456(89)90015-9 · Cited by 3,636
Final Version of the American Joint Committee on Cancer Staging System for Cutaneous Melanoma
Balch, C. M., Buzaid, A. C., Soong, S., Atkins, M. B., Cascinelli, N., Coit, D. G., Fleming, I. D., Gershenwald, J. E., Houghton, A. N., Kirkwood, J. M., et al. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.16.3635 · Cited by 2,627
iNOS-mediated nitric oxide production and its regulation
Aktan, F. (2004) · Life Sciences · doi:10.1016/j.lfs.2003.10.042 · Cited by 1,385
Management of Cutaneous Melanoma
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
de Vries, E., Bray, F., Coebergh, J. W. W., Parkin, D. M., & European Network of Cancer Registries (2003) · International Journal of Cancer · doi:10.1002/ijc.11360 · Cited by 384
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
Argininosuccinate synthetase from the urea cycle to the citrulline–NO cycle
Husson, A., Brasse‐Lagnel, C., Fairand, A., Renouf, S., & Lavoinne, A. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03559.x · Cited by 335
Eigentler, T., Caroli, U. M., Radny, P., & Garbe, C. (2003) · The Lancet Oncology · doi:10.1016/s1470-2045(03)01280-4 · Cited by 318
Incidence and distribution of argininosuccinate synthetase deficiency in human cancers
Dillon, B. J., Prieto, V. G., Curley, S. A., Ensor, M., Holtsberg, F. W., Bomalaski, J. S., & Clark, M. A. (2004) · Cancer · doi:10.1002/cncr.20057 · Cited by 317
Self-citationEnsor, M., Holtsberg, F. W., Bomalaski, J. S., & Clark, M. A. (2002) · PubMed · Cited by 315
Self-citationTapiero, H., Mathé, G., Couvreur, P., & Tew, K. D. (2002) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(02)00284-6 · Cited by 253
Izzo, F., Marra, P., Beneduce, G., Castello, G., Vallone, P., De Rosa, V., Cremona, F., Ensor, C. M., Holtsberg, F. W., Bomalaski, J. S., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.11.120 · Cited by 250
Self-citationCancer immunotherapy: The interferon-α experience
Kirkwood, J. M. (2002) · Seminars in Oncology · doi:10.1053/sonc.2002.33078 · Cited by 213
Holtsberg, F. W., Ensor, M., Steiner, M. R., Bomalaski, J. S., & Clark, M. A. (2002) · Journal of Controlled Release · doi:10.1016/s0168-3659(02)00042-1 · Cited by 155
Self-citationNew TNM melanoma staging system: Linking biology and natural history to clinical outcomes
Balch, C. M., Buzaid, A. C., Soong, S., Atkins, M. B., Cascinelli, N., Coit, D. G., Fleming, I. D., Gershenwald, J. E., Houghton, A. N., Kirkwood, J. M., et al. (2003) · Seminars in Surgical Oncology · doi:10.1002/ssu.10020 · Cited by 124
In vivo anti‐tumor activity of arginine deiminase purified from Mycoplasma arginini
Takaku, H., Takase, M., Abe, S., Hayashi, H., & Miyazaki, K. (1992) · International Journal of Cancer · doi:10.1002/ijc.2910510213 · Cited by 123
Clinical Trial Designs for the Early Clinical Development of Therapeutic Cancer Vaccines
Simon, R. M., Steinberg, S. M., Hamilton, M., Hildesheim, A., Khleif, S. N., Kwak, L. W., Mackall, C. L., Schlom, J., Topalian, S. L., & Berzofsky, J. A. (2001) · Journal of Clinical Oncology · doi:10.1200/jco.2001.19.6.1848 · Cited by 113
Systemic chemotherapy in the treatment of malignant melanoma
Lens, M. B., & Eisen, T. G. (2003) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.4.12.2205 · Cited by 98
Antiapoptotic role of endogenous nitric oxide in human melanoma cells.
Salvucci, O., Carsana, M., Bersani, I., Tragni, G., & Anichini, A. (2001) · PubMed · Cited by 97
Arginine deiminase: a potential inhibitor of angiogenesis and tumour growth
Is, P., Kang, S.-W., Shin, Y.-J., Chae, K.-Y., Park, M.-O., Kim, M. Y., Wheatley, D. N., & Min, B.-H. (2003) · British Journal of Cancer · doi:10.1038/sj.bjc.6601181 · Cited by 97
Takaku, H., Matsumoto, M., Misawa, S., & Miyazaki, K. (1995) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1995.tb03094.x · Cited by 89
Sugimura, K., Ohno, T., Kusuyama, T., & Azuma, I. (1992) · Melanoma Research · doi:10.1097/00008390-199209000-00007 · Cited by 83
Arginine Deiminase Inhibits Cell Proliferation by Arresting Cell Cycle and Inducing Apoptosis
Gong, H., Zölzer, F., Recklinghausen, G. V., Rössler, J. K., Breit, S., Havers, W., Fotsis, T., & Schweigerer, L. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1004 · Cited by 76
Wheatley, D. N. (2004) · Anti-Cancer Drugs · doi:10.1097/00001813-200410000-00002 · Cited by 74
Role of Nitric Oxide in Tumor Angiogenesis
Morbidelli, L., Donnini, S., & Ziche, M. (2004) · Cancer treatment and research · doi:10.1007/978-1-4419-8871-3_11 · Cited by 70
Gonzalez, G., & Byus, C. V. (1991) · PubMed · Cited by 69
Depletion of Dietary Arginine Inhibits Growth of Metastatic Tumor
Yeatman, T. J. (1991) · Archives of Surgery · doi:10.1001/archsurg.1991.01410350066010 · Cited by 67
Dillon, B. J., Holtsberg, F. W., Ensor, M., Bomalaski, J. S., & Clark, M. A. (2002) · PubMed · Cited by 58
Self-citationChen, T., Nines, R. G., Peschke, S. M., Kresty, L. A., & Stoner, G. D. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-0302 · Cited by 56
The Effect of Arginase on the Retardation of Tumour Growth
Bach, S. J., & Swaine, D. (1965) · British Journal of Cancer · doi:10.1038/bjc.1965.45 · Cited by 55
Gong, H., Pöttgen, C., Stüben, G., Havers, W., Stuschke, M., & Schweigerer, L. (2003) · International Journal of Cancer · doi:10.1002/ijc.11298 · Cited by 53
The best way to use asparaginase in childhood acute lymphatic leukaemia – still to be defined?
Pinheiro, J. P. V., & Boos, J. (2004) · British Journal of Haematology · doi:10.1111/j.1365-2141.2004.04863.x · Cited by 52
Noh, E. J., Kang, S. W., Shin, Y. J., Kim, D. C., Park, I. S., Kim, M. Y., Chun, B. G., & Min, B.-H. (2002) · Molecules and Cells · doi:10.1016/s1016-8478(23)15015-1 · Cited by 50
Holley, R. W. (1967) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(67)90076-7 · Cited by 43
Noh, E., Kang, S., Shin, Y., Choi, S., Kim, C., Park, I.-S., Wheatley, D. N., & Min, B. (2004) · International Journal of Cancer · doi:10.1002/ijc.20435 · Cited by 40
THOMAS, J. B., Holtsberg, F. W., Ensor, M., Bomalaski, J. S., & Clark, M. A. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630581 · Cited by 39
Self-citationOverview of melanoma vaccines: Active specific immunotherapy for melanoma patients
Ollila, D. W., Kelley, M. C., Gammon, G. M., & Morton, D. L. (1998) · Seminars in Surgical Oncology · doi:10.1002/(sici)1098-2388(199806)14:4 · Cited by 39
Takaku, H., Misawa, S., Hayashi, H., & Miyazaki, K. (1993) · Japanese Journal of Cancer Research · doi:10.1111/j.1349-7006.1993.tb02821.x · Cited by 38
Apoptotic cell death of human T lymphoblastoid cells induced by arginine deiminase.
Komada (1997) · International Journal of Hematology · doi:10.1016/s0925-5710(96)00538-5 · Cited by 36
The influence of arginine upon the growth rate of a transplantable tumour in the mouse
Gilroy, E. (1930) · Biochemical Journal · doi:10.1042/bj0240589 · Cited by 35
Regression of hepatocellular cancer in a patient treated with arginine deiminase.
Curley, S. A., Bomalaski, J. S., Ensor, M., Holtsberg, F. W., & Clark, M. A. (2003) · PubMed · Cited by 34
Self-citationTHOMAS, J. B., Holtsberg, F. W., Ensor, M., et al. (2002) · Biochemical Journal · doi:10.1042/bj3630581 · Cited by 34
Self-citationShen, L., Lin, W., Beloussow, K., Hosoya, K., Terasaki, T., Ann, D. K., & Shen, W. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00555-0 · Cited by 32
Pemetrexed: Single-agent and combination phase I study overview
Boyer, M. J., Rivory, L. P., & Clarke, S. J. (2002) · Seminars in Oncology · doi:10.1053/sonc.2002.37464 · Cited by 16
Update on the systemic treatment of malignant melanoma
Lawson, D. H. (2004) · Seminars in Oncology · doi:10.1053/j.seminoncol.2004.02.014 · Cited by 13
The systemic treatment of advanced cutaneous melanoma
Logan, T. F. (2003) · Facial Plastic Surgery Clinics of North America · doi:10.1016/s1064-7406(02)00056-1 · Cited by 10
Self-citationFeun, L. G., Savaraj, N., Hurley, J. E., & Marini, A. (2002) · Cancer Investigation · doi:10.1081/cnv-120001181 · Cited by 7
Self-citationThe role of biological response modifiers in malignant melanoma
Lens, M. B. (2003) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.3.8.1225 · Cited by 6
Adjuvant therapy of melanoma: what's new?
Ascierto, P. A., Palmieri, G., Daponte, A., Melucci, M. T., Satriano, R. A., Mozzillo, N., & Castello, G. (2002) · Melanoma Research · doi:10.1097/00008390-200206000-00015 · Cited by 4
Self-citationInhibitory effects of arginase on mammary adenocarcinoma transplants in strain "A" mice.
VRAT, V. (1951) · Permanente Foundation Medical Bulletin · Cited by 4
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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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