title: Clinical modulation of epirubicin resistance by lonidamine in patients with advanced soft-tissue sarcomas.
abstract: To determine if lonidamine (LND) could reverse anthracycline resistance In patients with advanced, soft-tissue sarcomas, thirty-six patients were treated with epirubicin (EPI) 120 mg/m(2) i.v. every 3 weeks. Progressive patients were given the same chemotherapy regimen on day 4 in combination with oral LND, 150 mg on day 1, 300 mg on day 2, and 450 mg on days 3 to 5. Among 35 evaluable patients there were 2 complete responses and 3 partial responses (PR) for an overall response rate of 14%. In the group treated with EPI+LND (24 evaluable patients) 2 PR were observed, lasting 3 and 10 months respectively. The overall survivall was 11.5 months. The most common side-effects were myelotoxicity, nausea and vomiting. Clinical cardiotoxicity was. not observed. Only in one patient a >20% decrease in LVEF from baseline was recorded. LND related toxicities were mild to moderate myalgia and photophobia. In a pharmacokinetic study performed parallel to the clinical study, no difference was observed between the parameters derived from EPI and EPI+LND curves except for Vapp. This study indicates that LND may circumvent clinical resistance in some cases without altering chemotherapy related toxicity.
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: S
authors.initials: S
authors.lastname: Carpano
authors.forename: L
authors.initials: L
authors.lastname: Dilauro
authors.forename: L
authors.initials: L
authors.lastname: Chiatti
authors.forename: P
authors.initials: P
authors.lastname: Vici
authors.forename: F
authors.initials: F
authors.lastname: Cavaliere
authors.forename: P
authors.initials: P
authors.lastname: Gentile
authors.forename: G
authors.initials: G
authors.lastname: Citro