Abstract
e18029 Background: Experimental evidence suggests that BRCA1 overexpression enhances sensitivity to docetaxel and resistance to cisplatin and RRM1 overexpression enhances resistance to gemcitabine. In order to further investigate the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced NSCLC, we performed this phase II clinical trial, testing the hypothesis that customized therapy would confer improved outcome over non-customized therapy. Methods: RNA was isolated from fresh tumor tissue. The chemotherapy regimen that patients received was based on their BRCA1 and RRM1 mRNA levels: both low, cisplatin plus gemcitabine (GP); both high novelbine plus cisplatin (NP); BRCA1 low and RRM1 high, cisplatin plus docetaxel (DP); BRCA1 high and RRM1 low, novelbine plus gemcitabine (GN). Results: From Dec 2005 to Nov 2008, 94 metastatic or local advanced NSCLC patients in our institute were enrolled into this study. The median age was 58 years old and 76% were male. Among them, 21 patients received GP, 30 patients received TP, 43 patients received NP and no patient received NP chemotherapy. GP group got a numerically higher response rate, longer median time to progression and median overall survival time than the other 2 group. The response rate in the GP,TP and NP group were 42.9%, 36.7% and 27.9% respectively (P=0.568), Median time to progression was 5.6,5.0,4.8 months (P=0.975)and median overall survival was 12.5, 11, 9.7 months (P=0.808) respectively. Conclusions: Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with numerically higher response rate and longer TTP and OS time in the GP group, which may be caused the controversial function of the BRCA1 and RRM1 mRNA at the initiation period of this trial, and suggested that BRCA1 and RRM1 mRNA levels could be used as biomarker in individual therapy in NSCLC. Efficacy of patients according to the treatment group. Regimen N Response TTP OS PR SD PD GP 21 9 9 3 5.6 12.5 TP 30 11 10 9 5.0 11 NP 43 12 19 12 4.8 9.7 Total 94 32 38 24 5 11 Abbreviations: PR, partial response; SD, stable disease; PD, progression disease.
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