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. 2012 Sep;24(3):226-31.
doi: 10.1007/s11670-012-0226-4.

Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

Sheng-Xiang Ren  1 , Ai-Wu Li, Song-Wen Zhou, Ling Zhang, Yong-Sheng Wang, Bing Li, Xiao-Xia Chen, Jie Zhang, Jian-Fang Xu, Cai-Cun Zhou
Affiliations

Individualized Chemotherapy in Advanced NSCLC Patients Based on mRNA Levels of BRCA1 and RRM1

Sheng-Xiang Ren et al. Chin J Cancer Res. 2012 Sep.

Abstract

Objective: Experimental evidence suggests that the overexpression of breast cancer-specific tumor suppressor protein 1 (BRCA1) gene enhances sensitivity to docetaxel and resistance to cisplatin and ribonucleotide reductase M1 (RRM1) gene overexpression enhances resistance to gemcitabine. To further examine the effect of BRCA1 and RRM1 mRNA levels on outcome in advanced non-small cell lung cancer (NSCLC), we performed this non-randomized phase II clinical trial which tested the hypothesis that customized therapy would confer improved outcome over non-customized therapy.

Methods: RNA was isolated from fresh tumor tissue. Patients received chemotherapy regimen based on their BRCA1 and RRM1 mRNA levels: both low-cisplatin plus gemcitabine (GP); both high-vinorelbine plus cisplatin (NP); BRCA1 low and RRM1 high-cisplatin plus docetaxel (TP); BRCA1 high and RRM1 low-vinorelbine plus gemcitabine (GN).

Results: From Dec 2005 to Nov 2008, 94 metastatic and locally advanced NSCLC patients from our institute were enrolled in this study. The median age was 58 years old. Among them, 21 patients received GP, 30 patients received TP and 43 patients received NP chemotherapy. GP group had a higher response rate, and longer median time to progression (TTP) and median overall survival (OS) time than the other 2 groups. The response rates in the GP, TP and NP groups were 42.9%, 36.7% and 27.9%, respectively (P=0.568). The median TTP was 5.6, 5.0, 4.8 months (P=0.975), respectively, and the median OS time was 12.5, 11.0, 9.7 months (P=0.808), respectively.

Conclusion: Chemotherapy customized according to BRCA1 and RRM1 expression levels is associated with higher response rate and longer TTP and OS time in the GP group. This suggests that BRCA1 and RRM1 mRNA levels could be used as biomarkers in individual therapy in NSCLC.

Keywords: BRCA1; Individualized chemotherapy; Non-small cell lung cancer; RRM1.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest: No potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1
Median TTP according to treatment groups in the 94 patients.
Figure 2
Figure 2
Median OS according to treatment groups in the 94 patients.
See this image and copyright information in PMC

References

    1. Chen WQ, Zhang SW, Zou XN, et al. Cancer incidence and mortality in China, 2006. Chin J Cancer Res 2011; 23:3-9 - PMC - PubMed
    1. Camps C, Sirera R, Iranzo V, et al. Gene expression and polymorphisms of DNA repair enzymes: cancer susceptibility and response to chemotherapy. Clin Lung Cancer 2007; 8:369-75 - PubMed
    1. Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002; 346:92-8 - PubMed
    1. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26:3543-51 - PubMed
    1. Ardizzoni A, Boni L, Tiseo M, et al. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 2007; 99:847-57 - PubMed