ArticleClinical epigenetics2015
Phase I study of azacitidine and oxaliplatin in patients with advanced cancers that have relapsed or are refractory to any platinum therapy.
Article in Clinical epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 16 citations in OpenAlex.
- Repurposing Azacitidine and Carboplatin to Prime Immune Checkpoint Blockade-resistant Melanoma for Anti-PD-L1 Rechallenge.Cancer research communications · 2022Trial
- Trial
- Article
- Cuproptosis-related genes and agents: implications in tumor drug resistance and future perspectives.Frontiers in pharmacology · 2025Review
- Article
- Review
- miR-454 promotes survival and induces oxaliplatin resistance in gastric carcinoma cells by targeting CYLD.Experimental and therapeutic medicine · 2020Article
- Differential Regulation of Methylation-Regulating Enzymes by Senescent Stromal Cells Drives Colorectal Cancer Cell Response to DNA-Demethylating Epi-Drugs.Stem cells international · 2018Article
- Prognostic and predictive significance of long interspersed nucleotide element-1 methylation in advanced-stage colorectal cancer.BMC cancer · 2016Article
- Article
- Article
- Epigenetic effects of RRx-001: a possible unifying mechanism of anticancer activity.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDemethylation process is necessary for the expression of various factors involved in chemotherapy cytotoxicity or resistance. Platinum-resistant cells may have reduced expression of the copper/platinum transporter CTR1. We hypothesized that azacitidine and oxaliplatin combination therapy may restore platinum sensitivity. We treated patients with cancer relapsed/refractory to any platinum compounds (3 + 3 study design) with azacitidine (20 to 50 mg/m(2)/day intravenously (IV) over 15 to 30 min, D1 to 5) and oxaliplatin (15 to 30 mg/m(2)/day, IV over 2 h, D2 to 5) (maximum, six cycles). Platinum content, LINE1 methylation (surrogate of global DNA methylation), and CTR1 expression changes (pre- vs. post-treatment) were assessed. Drug pharmacokinetics were analyzed.
resultsThirty-seven patients were treated. No dose-limiting toxicity (DLT) was noted at the maximum dose. The most common adverse events were anemia and fatigue. Two (5.4%) patients had stable disease and completed six cycles of therapy. Oxaliplatin (D2) and azacitidine (D1 and 5) mean systemic exposure based on plasma AUCall showed dose-dependent interaction whereby increasing the dose of oxaliplatin reduced the mean azacitidine exposure and vice versa; however, no significant differences in other non-compartmental modeled parameters were observed. Blood samples showed universal reduction in global DNA methylation. In tumor samples, hypomethylation was only observed in four out of seven patients. No correlation between blood and tumor demethylation was seen. The mean cytoplasmic CTR1 score decreased. The pre-dose tumor oxaliplatin levels ranged from <0.25 to 5.8 μg/g tumor. The platinum concentration increased 3- to 18-fold. No correlation was found between CTR1 score and oxaliplatin level, which was found to have a trend toward correlation with progression-free survival.
conclusionsOxaliplatin and azacitidine combination therapy was safe. CTR1 expression was not correlated with methylation status or tissue platinum concentration.
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