title: Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.
abstract: CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.
authors: Royal Marsden Hospital, London, UK. judson@icr.ac.uk
authors: I
authors: I
authors: Judson
authors: J A
authors: JA
authors: Radford
authors: M
authors: M
authors: Harris
authors: J Y
authors: JY
authors: Blay
authors: Q
authors: Q
authors: van Hoesel
authors: A
authors: A
authors: le Cesne
authors: A T
authors: AT
authors: van Oosterom
authors: M J
authors: MJ
authors: Clemons
authors: C
authors: C
authors: Kamby
authors: C
authors: C
authors: Hermans
authors: J
authors: J
authors: Whittaker
authors: E
authors: E
authors: Donato di Paola
authors: J
authors: J
authors: Verweij
authors: S
authors: S
authors: Nielsen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D012509:Sarcoma / Q000188:drug therapy* / Q000556:secondary; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin