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

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/m2 by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m2 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. © 2001 Elsevier Science Ltd.