P02 - Human equilibrative nucleoside transporter 1 as a predictor of efficacy to gemcitabine in advanced leiomyosarcoma and angiosarcoma

Abstract

Background: The expression of human equilibrative nucleoside transporter 1 (hENT1), the known major gemcitabine transporter into cells, has been thoroughly investigated as a predictive marker of response to gemcitabine in pancreatic cancer and biliary tract cancers. Since gemcitabine is also widely used in the treatment of leiomyosarcoma and angiosarcoma, we decided to investigate the correlation between the expression of hENT1 and gemcitabine efficacy in these sarcoma subtypes. Material (patients) and methods: We retrospectively identified 71 patients affected by advanced angiosarcoma (26) or leiomyosarcoma (45) treated within five Italian referral centers for sarcoma, whose tumor tissue was available; among them, 49 patients (15 angiosarcoma, 34 leiomyosarcoma) were treated with gemcitabine as single agent in first line chemotherapy. All tumor samples were analyzed for hENT1 expression by Real Time PCR. Median 2-?Ct value was used as the cut off to dichotomize patients into “high” expression and “low” expression groups. Kaplan Meier analysis was performed to estimate Time to Progression (TTP) and Overall Survival (OS). The correlation between hENT1 expression and TTP/OS was ascertained using the log- rank test. Results: We found a significant association between high hENT1 expression levels and favorable outcome in terms of TTP and OS compared to cases with low hENT1 expression in leiomyosarcoma treated with gemcitabine (TTP: 6.8 vs 3.2 months, P= 0.004; OS: 14.9 vs 8.5 months, P= 0.007). Additionally, hENT1 overexpression correlated with a significant improvement in TTP (9.3 vs 4.5 months; P= 0.02) and OS (20.6 vs 10.8 months; P= 0.001) in angiosarcoma patients treated with gemcitabine. Conclusions: Our study suggests that hENT1 expression is a predictive marker of efficacy both in patients with advanced leiomyosarcoma and angiosarcoma who received gemcitabine monotherapy. A prospective clinical trial in a larger series of patients is warranted to confirm these results.