Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL (R)/CAELYX (R)) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group

CAELYX (R) /DOXIL (R), pegylated liposomal doxorubicin, has shown antitumou r activity and reduced toxicity compared with standard doxorubicin in other tumour types, in this prospective randomised trial, 94 eligible patients w ith advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (R) (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with do xorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtype s were evenly matched, 33% were leiomyosarcoma (CAELYX (R): is. doxorubicin : 13). Primary disease sites were well matched. CAELYX (R) was significantl y less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia , versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) p atients given doxorubicin, but only 1 (2%) given CAELYX (R). 37 (86%) patie nts on doxorubicin had grade 2-3 alopecia, but only. 3 (6%) on CAELYX (R), and the major toxicity with CAELYX (R) was to the skin. Palmar-plantar eryt hrodysesthesia with CAELYX (R) was grade I. 4 (8%) patients, grade 2: 11 (2 2%) 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 (R): complete response (CR) 1 (uteri ne), 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 unkn own. but it may be due partly to a high proportion of gastrointestinal stro mal rumours. In conclusion. CAELYX (R) has equivalent activity to doxorubic in in STS with an improved toxicity profile and should be considered for fu rther investigation in combination with other agents such as ifosfamide. (C ) 2001 Elsevier Science Ltd. All rights reserved.