title: High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas--rationale for combination with radiotherapy.
abstract: Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth liposomal doxorubicin (Caelyx) is a novel drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy with Caelyx in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a total dose of 70 Gy. Caelyx was given as a 30-min infusion at a dose of 25 mg/m2 every 2 weeks. Scintigraphic imaging with Caelyx-99mTc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation compared to the surrounding healthy tissue. The regimen was well tolerated without any severe hematological or systemic toxicity. 'In field' radiation toxicity was not increased. Complete response was observed in 4/7 cases. It is concluded that combined chemo-radiotherapy with stealth liposomal doxorubicin for locally advanced sarcomas is feasible and promising, the benefit expected from the unique ability of the stealth liposomes to accumulate selectively in the tumoral tissue.
authors.affiliation: Department of Radiotherapy and Oncology, University Hospital of Iraklion, Crete, Greece. targ@her.forthnet.gr
authors.forename: M I
authors.initials: MI
authors.lastname: Koukourakis
authors.forename: S
authors.initials: S
authors.lastname: Koukouraki
authors.forename: A
authors.initials: A
authors.lastname: Giatromanolaki
authors.forename: S
authors.initials: S
authors.lastname: Kakolyris
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: A
authors.initials: A
authors.lastname: Velidaki
authors.forename: S
authors.initials: S
authors.lastname: Archimandritis
authors.forename: N N
authors.initials: NN
authors.lastname: Karkavitsas
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000532:radiotherapy*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin