High expression of topoisomerase-II predicts favorable clinical outcomes in patients with relapsed small cell lung cancers receiving amrubicin.

OBJECTIVES

Amrubicin monotherapy is a treatment option for patients with relapsed small cell lung cancers (SCLCs). Topoisomerase-II (Topo-II) - a target of amrubicin - has been reported as a predictive or prognostic marker for chemosensitivity or outcomes in patients with various malignancies. Here, we investigated the prognostic role of Topo-II expression in patients with relapsed SCLCs who underwent amrubicin monotherapy.

MATERIALS AND METHODS

Eighty-three patients with relapsed SCLCs who received amrubicin monotherapy between 2004 and 2015, after progression beyond first-line chemotherapy, were enrolled in the study. We retrospectively collected clinical data from their medical records, and evaluated the expression levels of Topo-II, by immunohistochemical staining of archival tumor specimens obtained through surgical resections or biopsies.

RESULTS

Most of the enrolled patients were elderly men (89%), with a median age of 70 years (range, 49-83); 16% of these patients showed Topo-II overexpression. Compared to patients with sensitive relapses, those with refractory relapses showed significantly higher Topo-II expression levels (P=0.03). The overall response rates in patients with high and low Topo-II expression were 38.5% and 25.7%, respectively (P=0.34). Multivariate analysis confirmed that patients with a higher Topo-II expression level had significantly longer progression-free survival (hazard ratio (HR), 0.39; P<0.01) and overall survival (HR, 0.48; P=0.04), compared to patients with a lower Topo-II expression level.

CONCLUSION

Our study identified Topo-II expression as a significant biomarker for the prediction of favorable outcomes in patients with relapsed SCLCs who underwent treatment with amrubicin, a Topo-II inhibitor. Thus, Topo-II expression may be a promising predictor of the efficacy of amrubicin.