Analysis of topoisomerase I expression and identification of predictive markers for efficacy of topotecan chemotherapy in small cell lung cancer

We evaluated topoisomerase I (TOPO1) expression in patients with small cell lung cancer (SCLC) and identified predictive factors for the efficacy of second-line topotecan chemotherapy.

TOPO1 expression was prevalent in SCLC patients. Strong expression was associated with an elevated disease control rate after second-line topotecan chemotherapy. Patients with sensitive disease that relapsed after first-line chemotherapy had better survival than refractory patients who received second-line topotecan chemotherapy.

We retrospectively evaluated the records of SCLC patients treated in our department from January 2007 to December 2016 who received second-line topotecan chemotherapy. Patients with archived tumor samples were enrolled. TOPO1 expression levels were evaluated by immunohistochemistry, and the relationships between TOPO1 expression, clinical factors, chemotherapy efficacy, and survival were analyzed.

Of the 78 patients enrolled, 67 showed TOPO1 expression (85.9%). Patients were divided into strong (n = 43) or weak (n = 35) expression groups based on staining intensity. Disease control rates for topotecan were 39.5% and 14.3% in the strong and weak groups, respectively (P = 0.014). Second-line median progression-free survival was 2.2 and 2.0 months (P = 0.057), and median overall survival was 8.1 and 6.0 months (P = 0.199) in the strong and weak positive groups, respectively. Patients were also divided into sensitive (n = 47) and refractory (n = 31) disease groups according to the duration from the onset of first-line therapy to relapse. Median second-line progression-free survival was 2.2 and 1.8 months in the sensitive and refractory relapse groups, respectively (P = 0.005). Conclusions: TOPO1 expression was prevalent in SCLC patients. Strong expression was associated with an elevated disease control rate after second-line topotecan chemotherapy. Patients with sensitive disease that relapsed after first-line chemotherapy had better survival than refractory patients who received second-line topotecan chemotherapy.