RRM1 and ERCC1 as biomarkers in patients with locally advanced and metastatic malignant pleural mesothelioma treated with continuous infusion of low-dose gemcitabine plus cisplatin

BackgroundMalignant Pleural Mesothelioma (MPM) is a rare but aggressive neoplasia that usually presents at advanced stages. Even though some advances have been achieved in the management of patients with MPM, this malignancy continuous to impose a deleterious prognosis for affected patients (12-18months as median survival, and 5-10% 5-year survival rate), accordingly, the recognition of biomarkers that allow us to select the most appropriate therapy are necessary.MethodsImmunohistochemistry semi-quantitative analysis was performed to evaluate four different biomarkers (ERCC1, RRM1, RRM2, and hENT-1) with the intent to explore if any of them was useful to predict response to treatment with continuous infusion gemcitabine plus cisplatin. Tissue biopsies from patients with locally advanced or metastatic MPM were analyzed to quantitatively asses the aforementioned biomarkers. Every included patient received treatment with low-dose gemcitabine (250mg/m(2)) in a 6-h continuous infusion plus cisplatin 35mg/m(2) on days 1 and 8 every 3 weeks as first-line therapy.ResultsFrom the 70 eligible patients, the mean and standard deviation (SD) for ERCC1, RRM1, RRM2 and hENT-1 were 286,178.3 ( 219, 019.8); 104,647.1 (+/- 65, 773.4); 4536.5 (+/- 5, 521.3); and 2458.7 (+/- 4, 983.4), respectively. Patients with high expression of RRM1 had an increased median PFS compared with those with lower expression (9.5 vs 4.8months, p=<0.001). Furthermore, high expression of RRM1 and ERCC1 were associated with an increased median OS compared with their lower expression counterparts; [(23.1 vs 7.2months for RRM1 p=<0.001) and (17.4 vs 9.8months for ERCC1 p=0.018)].Conclusions ERCC1 and RRM1 are useful biomarkers that predict better survival outcomes in patients with advanced MPM treated with continuous infusion of gemcitabine plus cisplatin.

Automated summary

The study conducted immunohistochemistry semi-quantitative analysis on four biomarkers (ERCC1, RRM1, RRM2, and hENT-1) to predict treatment response in advanced MPM patients receiving continuous infusion gemcitabine plus cisplatin, showing that ERCC1 and RRM1 are useful biomarkers for predicting better survival outcomes.