PHASE II STUDY ON GEMCITABINE IN ADVANCED TISSUE SARCOMAS OF THE ADULT

B. Švancárová, J-Y. Blay, I. Judson, O.S. Nielsen, Q. van Hoesel, A.T. van Oosterom, A. le Cesne, H.J. Keizer, C. Hermans, M. van Glabbeke, J. Verweij, EORTC Soft Tissue and Bone Sarcoma Group, and Data Center, Brussels, Belgium

Introduction: The objectives of this study were to assess the activity (objective response, and time to progression) and side effects of Gemcitabine in patients (pts) with advanced soft-tissue sarcomas, failing first line chemotherapy.

Methods: Gemcitabine was given as 30 minutes i.v. infusion at a dosage of 1250 mg/m² on day 1 and on day 8 in a 3 weekly schedule. A cycle was defined as a 3 weeks treatment period. Eligibility criteria included failure to respond to either one prior chemotherapy regimen or 2 single agents.

Results: 32 eligible patients entered the study. Median age was 54 (25-73 yrs). PS 0 : 11, 1 : 21. The predominant histological type was leiomyosarcoma 15 pts (47%). Six pts received one cycle, 12 pts two cycles, 2 pts three cycles, 4 pts four cycles and one patient 6 cycles of Gemcitabine. The hematological toxicities in 24 pts presently evaluable included WBC gr 3 2 pts (8%), neutropenia gr 3 3 pts (13%), gr 4 1 pt (4%), platelet gr 3 1 pt (4%), gr 4 1 pt (4%), hemoglobin gr 3-4 3 pts (13%). Non-hematological toxicities (23 pts presently evaluable) mainly involved mild to moderate nausea and vomiting. At present response data are available for 19 pts: PR 1, NC 4, PD 14 pts. The pt with PR had a high grade leiomyosarcoma relapsing in pleura and mediastinum following previous treatment with DOXO + IFO. The pleural and mediastinal regressed to PR after two cycles of Gemcitabine with further regression confirmed by CT-scan one month later.

Conclusion: Gemcitabine given at this dosage and schedule is not very effective in the treatment of patients with advanced soft-tissue sarcomas. Activity of Gemcitabine in certain sites of primary tumors and histological subtypes of soft-tissue sarcomas cannot yet be excluded (O. Merimsky et al., ASCO 1999, M.D. Anderson Hospital - personal comm.). Gemcitabine is worth studying in sarcoma patients failing first line chemotherapy, probably with prolonged administration (6-7 weeks) and maintenance therapy if at least disease stabilisation is achieved.