DOXIL® / CAELYX® HAS ANTITUMOUR ACTIVITY IN ADVANCED SOFT TISSUE SARCOMA WITH REDUCED TOXICITY COMPARED TO DOXORUBICIN. Results of a randomised phase II trial by the EORTC Soft Tissue and Bone Sarcoma Group (STBSG)

Judson I, Radford JA, Blay J-Y, van Hoesel Q, le Cesne A, van Oosterom A, Nielsen OS Kamby C, Woll P, Harris M, Hermans C, Donato di Paola E, Verweij J. STBSG and EORTC Data Center, Brussels, Belgium.

DOXIL® / CAELYX® (Doxil), pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin (dox) in other tumour types. 94 eligible patients with soft tissue sarcoma (STS) were treated in a randomised study, 50 with Doxil 50 mg/m² by 1 hr IV infusion q 4w, 44 with dox 75 mg/m² by IV bolus q 3w. Median age was Doxil: 52 yr, dox: 51 yr; PS scores on Doxil were: 0: 20, 1: 23, 2: 7; on dox: 0: 12, 1: 27, 2: 5, genders were Doxil: M: 26; F: 24 and dox: M: 20; F: 24. The usual range of histological subtypes was represented, 33% were leiomyosarcoma: - Doxil: 18; dox: 13, of which 70% were visceral - Doxil: 13; dox: 9. Primary disease sites were matched (uterine: Doxil 7; dox: 5; retroperitoneal: Doxil: 8; dox: 5; extremity or limb girdle Doxil: 15; dox: 12). Only 3 pts had prior adjuvant chemotherapy, 2 on Doxil, 1 on dox. Doxil was significantly less myelosuppressive, 6% pts with grade 3 & 4 neutropenia, v 77% on dox. 84% pts on dox had grade 2-3 alopecia, only 4% on Doxil. Other non-haematological grade 3 and 4 toxicities were rare. Stomatitis, nausea, vomiting and fatigue occurred equally with Doxil and dox. Grade 4 neutropenia occurred in 20 pts on dox (47%) and 1 pt on Doxil (2%), febrile neutropenia in 7 pts on dox (22.2%), only 1 on Doxil. The major toxicity with Doxil was skin, grades 2: 10 pts (20%), 3: 6 pts (12%), 4: 1 pt (2%). Ten pts on Doxil (21%) had hypersensitivity reactions, none on dox. Two pts stopped Doxil for skin toxicity, usually palmar-plantar erythrodysesthesia, a specific syndrome affecting hands, feet, pressure points and skin creases, causing painful exfoliation when severe. One pt stopped dox for cardiac toxicity. There were 38 deaths from disease progression and no treatment-related deaths. Confirmed responses were observed with both agents: Doxil: CR 1 (uterine), PR 3 (8.0%); and dox: CR 1, PR 3 (9.1%); with best response being stable disease in 15 and 18 patients respectively. The reason for the low response rate is unknown but it does not appear to be due to an excess of GI stromal tumours. DOXIL® /CAELYX® has equivalent activity to doxorubicin in STS with an improved toxicity profile.