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Predictive impact of RRM1 protein expression on vinorelbine efficacy in NSCLC patients randomly assigned in a chemotherapy phase III trial.
MedLine Citation:
PMID:  23038758     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BackgroundPlatinum-based doublets (PBDs) remain the cornerstone of treatment in non-small-cell lung cancer (NSCLC) and may include gemcitabine. A biomarker predicting sensitivity to this antimetabolite would represent a major step forward. Accordingly, we explored the predictive role of ribonucleotide reductase subunit M (RRM1) in advanced NSCLC.Patients and methodsA total of 443 patients were randomly assigned to regimen A [paclitaxel (Taxol) and cisplatin with gemcitabine] or regimen B (cisplatin and vinorelbine). Immunohistochemical evaluation of RRM1 was correlated to clinical end-points.ResultsA total of 261 (58.9%) patients had representative tissue samples for RRM1 evaluation. Disease control rate, progression-free survival (PFS) and overall survival (OS) were substantially improved in patients with RRM-negative (neg) tumors receiving regimen B when compared with patients with RRM-positive (pos) tumors (68.8% versus 31.2%, P = 0.046, 6.90 months versus 3.93 months, P = 0.000 and 11.57 months versus 7.4 months, P = 0.002, respectively). Interaction analysis between RRM1-neg status and adenocarcinomas yielded a hazard ratio (HR) of 0.36 for death (P = 0.000).ConclusionsRRM1 protein expression was without any predictive impact in patients treated with cisplatin, paclitaxel and gemcitabine. Surprisingly, the predictive power was demonstrated in the cisplatin and vinorelbine arm and may suggest that RRM1 is involved in vinorelbine sensitivity warranting further research.
Authors:
A C Vilmar; E Santoni-Rugiu; J B Sorensen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-4
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  -     ISSN:  1569-8041     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Oncology 5073, Finsen Centre, Copenhagen.
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