ArticlePloS one2016
Cell Line Derived 5-FU and Irinotecan Drug-Sensitivity Profiles Evaluated in Adjuvant Colon Cancer Trial Data.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- Article
- Molecular Biomarker of Drug Resistance Developed From Patient-Derived Organoids Predicts Survival of Colorectal Cancer Patients.Frontiers in oncology · 2022Article
- Predicting efficacy of epirubicin by a multigene assay in advanced breast cancer within a Danish Breast Cancer Cooperative Group (DBCG) cohort: a retrospective-prospective blinded study.Breast cancer research and treatment · 2018Article
- Molecular prediction of adjuvant cisplatin efficacy in Non-Small Cell Lung Cancer (NSCLC)-validation in two independent cohorts.PloS one · 2018Article
- Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.Molecular therapy oncolytics · 2017Article
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Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis study evaluates whether gene signatures for chemosensitivity for irinotecan and 5-fluorouracil (5-FU) derived from in vitro grown cancer cell lines can predict clinical sensitivity to these drugs.
methodsTo test if an irinotecan signature and a SN-38 signature could identify patients who benefitted from the addition of irinotecan to 5-FU, we used gene expression profiles based on cell lines and clinical tumor material. These profiles were applied to expression data obtained from pretreatment formalin fixed paraffin embedded (FFPE) tumor tissue from 636 stage III colon cancer patients enrolled in the PETACC-3 prospective randomized clinical trial. A 5-FU profile developed similarly was assessed by comparing the PETACC-3 cohort with a cohort of 359 stage II colon cancer patients who underwent surgery but received no adjuvant therapy.
resultsThere was no statistically significant association between the irinotecan or SN-38 profiles and benefit from irinotecan. The 5-FU sensitivity profile showed a statistically significant association with relapse free survival (RFS) (hazard ratio (HR) = 0.54 (0.41-0.71), p<1e-05) and overall survival (HR = 0.47 (0.34-0.63), p<1e-06) in the PETACC-3 subpopulation. The effect of the 5-FU profile remained significant in a multivariable Cox Proportional Hazards model, adjusting for several relevant clinicopathological parameters. No statistically significant effect of the 5-FU profile was observed in the untreated cohort of 359 patients (relapse free survival, p = 0.671).
conclusionThe irinotecan predictor had no predictive value. The 5-FU predictor was prognostic in stage III patients in PETACC-3 but not in stage II patients with no adjuvant therapy. This suggests a potential predictive ability of the 5-FU sensitivity profile to identify colon cancer patients who may benefit from 5-FU, however, any biomarker predicting benefit for adjuvant 5-FU must be rigorously evaluated in independent cohorts. Given differences between the two study cohorts, the present results should be further validated.
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