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RESEARCH PRODUCT

Trabectedin-Related Liver Toxicity in Soft Tissue Sarcoma Patients: Always a Good Reason to Discontinue the Treatment?

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ABSTRACT Aim: A transient increase in liver enzymes is a well described side effect developed by almost 40% of soft tissue sarcoma (STS) patients treated with trabectedin, often leading to treatment delays or discontinuation. We retrospectively analysed the correlation between trabectedin-related liver toxicity and treatment outcome. Methods: Data from a total of 113 patients receiving trabectedin administered at the dose of 1.5 mg/m2 iv 24 hours in 3 reference centers were evaluated. This exploratory analysis was performed to assess the impact of liver toxicity (grade 3-4 AST and ALT increases) on the trabectedin efficacy and outcome in STS patients. All the patients included had metastatic disease or locally advanced inoperable and received at least one previous line of treatment containing anthracycline. All patients received standard steroids premedication. Results: Median age was 57 years (range: 27-79 ys) and male/female ratio was 71/42. STS histologies were: liposarcoma 32 cases, leiomiosarcoma 27, pleomorphic sarcoma 17, synovial sarcoma 13, 24 other histologies. For 45 patients a G3-4 ALT increase in the first two cycles was reported while for 68 was not. Calculations show that hazard ratios for PFS and OS are not statistically significant (HR=1.124; p=0.734 and HR=0.104; p=0.850, respectively). Furthermore, the analysis was repeated dividing the population between patients with G3-4 ALT elevation during treatment vs. patients without such elevation. Again, hazard ratios for PFS and OS are not statistically significant (HR=0.791; p=0.309 and HR=0.930; p=0.810930, respectively). Finally, the analyses was repeated, splitting the population in patients with peak>15 ULN vs. patients with peak Conclusions: Liver toxicity is a common event during treatment with trabectedin and does not affect outcome. These results should discourage the premature discontinuation of the drug due to the increase in liver enzymes. Disclosure: All authors have declared no conflicts of interest.