Dataset Information

The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.

ABSTRACT: Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanMethylation450 array. Association tests were adjusted for confounders, including proxies for leukocyte cell counts. There were substantial methylation differences between these two groups that vanished once the leukocyte heterogeneity was accounted for. We observed a significant decrease of T cells in the treatment group (CD4+: p=10(-6); CD8+: p=0.036) and significant increase of NK cells (p=0.05) and monocytes (p=0.0006). 5-FU/leucovorin has no effect on global and local blood-based methylation profiles, other than through differences in the leukocyte compositions that the treatment induced.

SUBMITTER: Lemire M

PROVIDER: S-EPMC4722538 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.

Lemire Mathieu M Zaidi Syed H E SH Zanke Brent W BW Gallinger Steven S Hudson Thomas J TJ Cleary Sean P SP

Genomics 20150911 6

Blood-based epigenome-wide association studies that aim at comparing CpG methylation between colorectal cancer (CRC) patients and controls can lead to the discovery of diagnostic or prognostic biomarkers. Numerous confounders can lead to spurious associations. We aimed to see if 5-fluorouracil (5-FU)/leucovorin chemotherapy administered to cases prior to the collection of their blood has an effect on methylation. 304 patients who received treatment and 273 who did not were profiled on the HumanM ...[more]

PMID: 26368860

Similar Datasets

Project description:ImportancePerioperative chemotherapy is a potential treatment for locally advanced gastric cancer. However, the optimal chemotherapy regimen remains unknown.ObjectiveTo investigate the safety and efficacy of S-1 plus oxaliplatin (SOX) vs fluorouracil, leucovorin, and oxaliplatin (FOLFOX) as a perioperative chemotherapy regimen for patients with locally advanced gastric cancer.Design, setting, and participantsIn this phase 3, open-label, multicenter, randomized clinical trial, patients from 12 Chinese hospitals were enrolled between June 2011 and August 2016, with a last follow-up date of September 2019. The primary tumor was evaluated as either invading the serosa or the adjacent structures with or without metastatic lymph nodes, and with no evidence of distant metastases. Data were analyzed from December 2019 to June 2020.InterventionsPatients were randomly assigned (1:1) to receive either 6 perioperative (2-4 preoperative and 2-4 postoperative) 3-week cycles of 130 mg/m2 oxaliplatin on day 1 and 80 to 120 mg/d S-1 orally daily for 2 weeks (SOX) or 130 mg/m2 oxaliplatin, 400 mg/m2 fluorouracil, 400 mg/m2 leucovorin, and 2400 mg/m2 fluorouracil as 46-hour infusion on day 1 (FOLFOX).Main outcomes and measuresThe primary end point was 3-year overall survival (OS). An absolute noninferiority margin of -8% was chosen.ResultsA total of 583 patients were enrolled; 293 were randomized to the SOX group and 290 were randomized to the FOLFOX group. Twelve patients (2.1%) refused preoperative chemotherapy (5 patients in the SOX group and 7 patients in the FOLFOX group), leaving a total of 288 patients in the SOX group (median [range] age, 61 [24 to 78] years; 197 men [68.4%]) and 283 patients in the FOLFOX group (median [range] age, 62 [24 to 80] years; 209 men [73.9%]) who received preoperative chemotherapy. The 3-year OS rate was 75.2% (95% CI, 70.3% to 80.5%) in the SOX group and 67.8% (95% CI, 62.5% to 73.5%) in the FOLFOX group. The absolute difference of 3-year OS rate between the 2 groups was 7.4% (95% CI, -0.1% to 14.9%), which was greater than the prespecified noninferiority margin (-8%) and showed the noninferiority of perioperative chemotherapy with SOX compared with FOLFOX.Conclusions and relevanceIn this randomized clinical trial, SOX was noninferior to FOLFOX as perioperative chemotherapy for patients with locally advanced gastric cancer and could be recommended as an alternative treatment for these patients in Asia.Trial registrationClinicalTrials.gov Identifier: NCT01364376.

Project description:IntroductionLiposomal irinotecan (nal-IRI) plus fluorouracil/leucovorin (5-FU/LV) has shown clinical benefit in patients with metastatic pancreatic adenocarcinoma (mPAC) who progressed on gemcitabine-based chemotherapy. However, its role in patients with mPAC previously treated with conventional irinotecan-containing chemotherapy has not been appropriately investigated.MethodsIn this retrospective analysis, patients with mPAC who received nal-IRI plus 5-FU/LV after conventional irinotecan-containing regimen between January 2017 and March 2020, were identified from two referral cancer centers in South Korea. The ratio of time to progression (TTP) with nal-IRI plus 5-FU/LV to TTP with conventional irinotecan (TTPr) was analyzed with respect to the duration and cumulative dose of conventional irinotecan treatment.ResultsIn total, 35 patients treated with nal-IRI plus 5-FU/LV after the irinotecan-containing regimen were analyzed. The median age was 58 years and 16 (46%) patients were male. The median duration of conventional irinotecan therapy was 4.6 months at a median cumulative dose of 1230 mg. The objective response rate of nal-IRI plus 5-FU/LV was 2.9%, and stable disease was achieved in 11 (31.4%) patients. During the median follow-up of 9.2 [95% confidence interval (CI): 7.8-10.5] months, the median progression-free survival (PFS) and overall survival (OS) were 2.0 (95% CI: 1.4-2.6) months and 4.4 (95% CI: 3.6-5.7) months, respectively. The 6-month PFS and OS rates were 16.3% and 37.5%, respectively. The median TTPr was 0.41 (range, 0.07-2.07), showing a negative correlation with the cumulative dose of prior irinotecan therapy (R = -0.37, p = 0.041). A tentative negative correlation between TTPr and duration of prior irinotecan therapy was observed (R = -0.35, p = 0.062). The most common grade 3-4 toxicities were neutropenia (20%) and fatigue (8.6%).ConclusionNal-IRI plus 5-FU/LV showed modest effectiveness and manageable toxicities for patients with mPAC previously treated with conventional irinotecan-containing chemotherapy. The cumulative dose of prior conventional irinotecan therapy may be inversely correlated with the effectiveness of nal-IRI plus 5-FU/LV.

Dataset Information

The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.

Publications

The effect of 5-fluorouracil/leucovorin chemotherapy on CpG methylation, or the confounding role of leukocyte heterogeneity: An illustration.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets