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PurposeNo chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 (ERCC1) gene has been related to cisplatin activity.Experimental designPatients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method.ResultsA total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P < 0.001). In the gemcitabine/cisplatin arm, patients with low RRM1 mRNA expression levels had significantly longer median survival than those with high levels [13.7 versus 3.6 months; 95% confidence interval (CI), 9.6-17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6-11.1 months; P = 0.016).ConclusionsRRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.

Original publication

DOI

10.1158/1078-0432.ccr-03-0156

Type

Journal article

Journal

Clinical cancer research : an official journal of the American Association for Cancer Research

Publication Date

02/2004

Volume

10

Pages

1318 - 1325

Addresses

Medical Oncology Service, Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Barcelona, Spain. rrosell@ns.hugtip.scs.es

Keywords

Spanish Lung Cancer Group, Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Cisplatin, Endonucleases, Ribonucleotide Reductases, Ribonucleoside Diphosphate Reductase, DNA-Binding Proteins, Tumor Suppressor Proteins, DNA, RNA, Messenger, Deoxycytidine, Antineoplastic Agents, Antimetabolites, Antineoplastic, Prognosis, Treatment Outcome, DNA Repair, Time Factors, Adult, Aged, Middle Aged, Female, Male