title: Lack of Correlation Between Liver Tests Abnormalities and Trabectedin Efficacy in the Treatment of Soft Tissue Sarcoma: a Retrospective Study.
abstract: Elevation in liver transaminases is common in patients treated with the marine antitumor agent trabectedin. However, the impact of trabectedin-related transaminase elevations on treatment outcomes is unclear. This retrospective study investigated the correlation between liver tests abnormalities and treatment outcomes in patients with unresectable advanced or metastatic soft tissue sarcomas (STS) treated with trabectedin 1.5 mg/m(2) once every 3 weeks at three reference centers in Italy. The effect of grade 3/4 elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) during the first two cycles and at any time during trabectedin treatment on progression-free survival (PFS) and overall survival (OS) were analyzed. Liver tests abnormalities during the first two cycles of chemotherapy or at any time during trabectedin treatment did not significantly affect PFS or OS. Nor were survival outcomes significantly different in the subgroups of patients with or without ALT/AST increases or with ALT/AST elevations ≥ 15 × the upper limit of normal (ULN) versus those with ALT/AST elevation < 15 × ULN. Although liver tests abnormalities are common in patients treated with trabectedin, elevations in ALT and AST are usually transient, occur during the first two cycles of treatment, and do not appear to affect survival.
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Stumbo
authors.affiliation: Department of Medical Oncology, Policlinico P. Giaccone, Palermo, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Maltese
authors.affiliation: Medical Oncology, Ospedale San Camillo Forlanini, Rome, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Cerbone
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Spalato Ceruso
authors.affiliation: Department of Medical Oncology, Policlinico P. Giaccone, Palermo, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Badalamenti
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tonini
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Frezza
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: De Lisi
authors.affiliation: Medical Oncology, University campus Bio-Medico, Rome, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Silletta
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001219:Aspartate Aminotransferases; D004149:Dioxoles / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008099:Liver / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D044005:Tetrahydroisoquinolines; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000077606:Trabectedin