{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:51:22Z","timestamp":1792291882714,"version":"4.4.0"},"reference-count":33,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,11,28]],"date-time":"2021-11-28T00:00:00Z","timestamp":1638057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Arginine depletion interferes with pyrimidine metabolism and DNA damage repair pathways. Preclinical data demonstrated that depletion of arginine by PEGylated arginine deiminase (ADI\u2010PEG 20) enhanced liposomal doxorubicin (PLD) cytotoxicity in cancer cells with argininosuccinate synthase 1 (ASS1) deficiency. The objective of this study was to assess safety and tolerability of ADI\u2010PEG 20 and PLD in patients with metastatic solid tumors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with advanced ASS1\u2010deficient solid tumors were enrolled in this phase 1 trial of ADI\u2010PEG 20 and PLD following a 3\u00a0+\u00a03 design. Eligible patients were given intravenous PLD biweekly and intramuscular (IM) ADI\u2010PEG 20 weekly. Toxicity and efficacy were evaluated according to the Common Terminology Criteria for Adverse Events (version 4.0) and Response Evaluation Criteria in Solid Tumors (version 1.1), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of 15 enrolled patients, 9 had metastatic HER2\u2010negative breast carcinoma. We observed no dose\u2010limiting toxicities or treatment\u2010related deaths. One patient safely received 880\u00a0mg\/m<jats:sup>2<\/jats:sup> PLD in this study and 240\u00a0mg\/m<jats:sup>2<\/jats:sup> doxorubicin previously. Treatment led to stable disease in 9 patients and was associated with a median progression\u2010free survival time of 3.95\u00a0months in 15 patients. Throughout the duration of treatment, decreased arginine and increased citrulline levels in peripheral blood remained significant in a majority of patients. We detected no induction of anti\u2010ADI\u2010PEG 20 antibodies by week 8 in one third of patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Concurrent IM injection of ADI\u2010PEG 20 at 36\u00a0mg\/m<jats:sup>2<\/jats:sup> weekly and intravenous infusion of PLD at 20\u00a0mg\/m<jats:sup>2<\/jats:sup> biweekly had an acceptable safety profile in patients with advanced ASS1\u2010deficient solid tumors. Further evaluation of this combination is under discussion.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.4446","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T05:37:07Z","timestamp":1638164227000},"page":"340-347","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Phase 1 trial of ADI\u2010PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors"],"prefix":"10.1002","volume":"11","author":[{"given":"Shuyang","family":"Yao","sequence":"first","affiliation":[{"name":"Department of Investigational Cancer Therapeutics  Houston Texas USA"},{"name":"Department of Thoracic Surgery Xuanwu Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Janku","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Breast Medical Oncology  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2713-233X","authenticated-orcid":false,"given":"Apostolia Maria","family":"Tsimberidou","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina Anne","family":"Piha\u2010Paul","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Investigational Cancer Therapeutics  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Pathology The University of Texas MD Anderson Cancer Center  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Johnston","sequence":"additional","affiliation":[{"name":"Polaris Pharmaceuticals, Inc.  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