Connective Tissue Oncology Society

2001 CTOS Annual Meeting Posters— Medical Oncology

ET-743, A NEW ACTIVE DRUG IN ADULT SOFT TISSUE SARCOMA: A SOFT-TISSUE AND BONE SARCOMA GROUP /EORTC PHASE II TRIAL
Axel Le Cesne¹, Jean Yves Blay¹, Ian Judson¹, Alan Van Oosterom¹, Jaap Verweij¹, John Radford¹, Paul Lorigan¹, Elisabeth Gray¹, Jose Jimeno², Ole Nielsen¹
¹STBSG - EORTC Data Center, ²Pharma Mar

OBJECTIVE: The main objectives of this multicenter phase II study were to assess the activity and toxicity of ET-743 (Pharma Mar/Spain) administered at a dose of 1500 g/m2 as 24-hour CI every 3 weeks in patients (pts) with advanced sarcoma.

METHODS: Pts with GIST (group (gp) B) received ET-743 as front-line chemotherapy (CT) while pts with documented progressive STS (gp A and C) as 2nd/3rd line CT. Evaluation of response in gp C was performed with the new system based on RECIST criteria

RESULTS: between 5/99 and 11/00, 471 cycles of ET-743 were administered to 132 pts (47, 28 and 57 in gp A, B and C respectively). Toxicity (T) : there was no alopecia and no severe digestive T. A reversible gde 3-4 transient elevation of transaminases was seen in about 40% of pts in all gps. Febrile neutropenia (N) and gde 3-4 N were observed in 15, 7 and 3% and 45, 48 and 58% of pts included in gps A, B and C respectively. Haematological T was not cumulative (pts receiving from 1 to 14 cycles). There were 4 toxicity-related deaths in gp A. After protocol amendment (10/99) requiring normal ALP at inclusion and ET-743 dose reduction (1200 g/m2) in case of an intercycle-rise in bil/ALP, the incidence of serious T has been significantly decreased. No OR were observed in GIST pts. Among the 94 eligible pts in gp A and C, there were 8 PR (OR rate of 9%), 48 NC (51%) (including 4 not confirmed PR and 2 prolonged major MR) and 28 PD (30%). Two patients are ongoing and 8 pts were not evaluable. The 6 months progression free survival (6PFS) for all included pts were 31, 24 and 28% in gp A, B and C respectively. Thirty six pts received at least 6 cycles of CT. The 6PFS observed in non-GIST sarcoma compares favorably with those (6PFS: 18%) obtained with other active drugs tested in 2nd line CT in previous EORTC trials (Van Glabbeke, ASCO 01). Median overall survival was 250 and 241 days for pts included in gp A and C respectively

CONCLUSION: ET-743 is an active compound in advanced STS. Further studies with a shorter infusion time as single agent and/or in combination are warranted.