Expression of ERCC1, RRM1 and LRP in non-small cell lung cancers and their influence on chemotherapeutic efficacy of gemcitabine concomitant with nedaplatin.

Zhen-Qin Qiu,Kun Zhao

doi:10.7314/apjcp.2014.15.17.7303

Abstract

To explore the clinical efficacy of gemcitabine concomitant with nedaplatin and drug resistance in the treatment of non-small cell lung cancer (NSCLC) and associated molecular predicators. A total of 68 patients diagnosed with NSCLC by histology served as the study objects and were randomly divided into an observation group treated with gemcitabine concomitant with nedaplatin and a control group with cisplatin concomitant with gemcitabine, 34 cases for each group. Short-term and long-term efficacies, adverse responses as well as the expression of nucleotide excision repair cross complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1) and lung resistance-related protein (LRP) in NSCLC tissues in both groups were assessed. The short-term objective response rate (ORR) and disease control rate (DCR) were 35.3% (12/34) and 76.5% (26/34) in the observation group and 38.2% (13/34) and 85.3% (29/34) in the control group, respectively, the differences not being statistically significant. The time to progression (TTP) in both groups were 1~12 months, while the median TTP was 135 d and 144 d, respectively. Though the survival was slightly higher in the control group, there were no significant differences in TTP and survival time. The rates of decreased hemoglobin, vomiting and nausea as well as renal toxicity were evidently lower in the observation group, while other adverse responses demonstrated no significant difference. The positive expression rates of ERCC1, RRM1 and LRP were 47.1% (16/34), 61.8% (21/34) and 64.7% (22/34) in the observation group, respectively. Compared with negative ERCC1 expression, ORR had decreasing trend and the overall survival time (OS) decreased significantly in patients with positive ERCC1 expression, which were markedly decreased by the positive expressions of RRM1 and LRP. Gemcitabine concomitant with nedaplatin has significant effects in the treatment of NSCLC, with an adverse response rate obviously lower than for cisplatin concomitant with gemcitabine, suggesting that wider use in the clinic is warranted. Additionally, the positive expressions of ERCC1, RRM1 and LRP may increase patient drug resistance, so they can be applied as the chemotherapeutic predicators to guide individualized therapy of NSCLC patients.

Highlights

Non-small cell lung cancer (NSCLC), as a common malignant tumor accounting for 80%~85% in all lung cancers, is characterized by higher morbidity, dormant onset, rapid development and short survival time, etc., in which 80% of patients have lost the optimal operative opportunities when diagnosed (Siegel et al, 2012)
Complete response (CR), Partial response (PR), Stable disease (SD), Progressive disease (PD), objective response rate (ORR) and disease control rate (DCR) were 2.94% (1/34), 32.35% (11/34), 41.18% (14/34), 23.53% (8/34), 35.29% (12/34) and 76.47% (26/34) in observation group and were 2.94% (1/34), 35.29% (12/34), 47.06% (16/34), 14.71% (5/34), 38.24% (13/34) and 85.29% (29/34) in control group, respectively, but there was no significant difference in ORR (χ2=0.0633, P=0.8014) and DCR (χ2=0.8559, P=0.3549)
It was reported that the medium overall survival time (OS) of single gemcitabine was 8 months (Valle et al, 2010; Ueno et al, 2013), but the effective response and OS could both be markedly improved by gemcitabine combined with platinums

Summary

Introduction

Non-small cell lung cancer (NSCLC), as a common malignant tumor accounting for 80%~85% in all lung cancers, is characterized by higher morbidity, dormant onset, rapid development and short survival time, etc., in which 80% of patients have lost the optimal operative opportunities when diagnosed (Siegel et al, 2012). The primary therapies for NSCLC patients are chemotherapies, in which the platinum-based ones are best in efficacy. They are always accompanied with severe gastrointestinal responses as well as renal and hematological toxicities. Since the development of new-type anti-tumor drugs, the double-drug protocols of the third generation of antitumor chemotherapeutical drugs gemcitabine combined with platinums have become the standard first-line treatments for NSCLC patients with decreased adverse responses to some extent. It is probable that the application of NSCLC drug resistance associated biological predicators to predicate the chemotherapeutic efficacy can apparently improve the therapeutic effective rate and prognosis as well as obviously reduce the unnecessary adverse responses and financial burdens so as to realize the individualized therapies for NSCLC patients. Gemcitabine combined with cisplatin was applied as control group to explore the clinical efficacy and adverse responses of gemcitabine concomitant with nedaplatin and detect the expressions

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Results

Conclusion