ArticleBritish journal of cancer2021
Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies.
Article in British journal of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Metabolic rewiring of the dendritic cell-T cell axis: tumour-derived barriers and therapeutic opportunities.Experimental & molecular medicine · 2026Review
- Context-dependent synthetic lethality - an emerging precision therapeutic approach.Nature reviews. Cancer · 2026Review
- Targeting arginine metabolism overcomes chemotherapy resistance in aggressive-variant prostate cancers.iScience · 2026Article
- Review
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Molecular mechanisms and therapies for tumor inhibition through the arginine metabolism pathway.Frontiers in oncology · 2026Review
- Metabolic Reprogramming of Cancer Cells and Therapeutics Targeting Cancer Metabolism.Cancer medicine · 2025Review
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Urea cycle dysregulation: a new frontier in cancer metabolism and immune evasion.Cell communication and signaling : CCS · 2025Review
- PEGylated RecombinantACS biomaterials science & engineering · 2024Article
- Amino acid metabolism in tumor biology and therapy.Cell death & disease · 2024Review
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Dietary Manipulation of Amino Acids for Cancer Therapy.Nutrients · 2023Review
- The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C.Cancer cell international · 2023Article
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Metabolic reprogramming of clear cell renal cell carcinoma.Frontiers in endocrinology · 2023Review
- Hybrid Silica-Coated PLGA Nanoparticles for Enhanced Enzyme-Based Therapeutics.Pharmaceutics · 2022Article
- Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives.Cancer research · 2022Review
- Artificial Diets Based on Selective Amino Acid Restriction versus Capecitabine in Mice with Metastatic Colon Cancer.Nutrients · 2022Article
- A Phase 1 study of ADI-PEG20 (pegargiminase) combined with cisplatin and pemetrexed in ASS1-negative metastatic uveal melanoma.Pigment cell & melanoma research · 2022Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundArginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.
methodsThis single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.
resultsWe enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).
conclusionConcurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.