title: Steroid premedication markedly reduces liver and bone marrow toxicity of trabectedin in advanced sarcoma.
abstract: Trabectedin is a marine-derived cytoxic alkaloid which has shown promising antitumour activity in a variety of human malignancies including sarcoma. Fifty-four patients with advanced sarcoma (age 43 yrs, range 18-70), all pretreated with prior chemotherapy, were enrolled on a named individual basis for treatment with trabectedin. Diagnosis was adult soft tissue sarcoma (STS) in 46 patients, Ewing's family tumour (EFT) in 4, and osteosarcoma (OS) in 4. The initial 23 patients (total number of courses administered: 68) did not receive premedication prior to trabectedin, while the other 31 patients (total number of courses administered: 134) received premedication with dexamethasone 4 mg po bid 24 hours before therapy. Incidence of toxicity (grade 3-4), expressed as percentage of courses, was as follows: in patients without dexamethasone, elevation of transaminases 34%, neutropenia 24% and thrombocytopenia 25%; in patients with prior dexamethasone, elevation of transaminases 2%, neutropenia 2% and no thrombocytopenia. The median received dose intensity of trabectedin was superimposable in the two groups (404 microg and 400 microg per week, respectively), as well as progression-free survival (19% at 6 months). Among STS patients, 9% had objective responses. In this unselected patient series, premedication with dexamethasone strongly reduced drug-induced hepatotoxicity and myelosuppression.
authors.affiliation: Cancer Medicine Dept., Adult Sarcoma Medical Oncology Unit, Istituto Nazionale Tumori, Via G. Venezian 1, 20133 Milano, Italy. federica.grosso@istitutotumori.mi.it
authors.forename: F
authors.initials: F
authors.lastname: Grosso
authors.forename: P
authors.initials: P
authors.lastname: Dileo
authors.forename: R
authors.initials: R
authors.lastname: Sanfilippo
authors.forename: S
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: R
authors.initials: R
authors.lastname: Bertulli
authors.forename: C
authors.initials: C
authors.lastname: Piovesan
authors.forename: J
authors.initials: J
authors.lastname: Jimeno
authors.forename: M
authors.initials: M
authors.lastname: D'Incalci
authors.forename: A
authors.initials: A
authors.lastname: Gescher
authors.forename: P G
authors.initials: PG
authors.lastname: Casali
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001855:Bone Marrow Diseases / Q000139:chemically induced* / Q000517:prevention & control; D056486:Chemical and Drug Induced Liver Injury; D004149:Dioxoles / Q000009:adverse effects*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D011292:Premedication; D012509:Sarcoma / Q000188:drug therapy*; D013256:Steroids / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines / Q000009:adverse effects*; D000077606:Trabectedin
chemical_list: D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D013256:Steroids; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin