857 Increasing continuous infusion (C.I.) ifosfamide (IFO) and bolus epirubicin (EPI) in soft tissue sarcoma (STS) patients (PTS)

Abstract

There is a direct relationship between the dose of IFO and EPI and the clinical response achievable in STS. We have, therefore, associated full doses of EPI (60 mg/m2 × 2 d, 1 hr inf.) to increasing c.i. IFO + MESNA and G-CSF (300 μg/d, +7 to +14) in order to evaluate the maximum tolerated dose (MTD) of this program and obtain information on the clinical activity. The IFO starting dose level was 9 g/m2 (72 hrs c.i.); further planned levels are 10.5 g/m2 (84 hrs) and 12 g/m2 (96 hrs). Eval for the definition of the MTD are those pts completing 3 consecutive cycles or developing a DLT. A DLT corresponded to: a G4 leucopenia or thrombocytopenia ≥ 5 day; any G3 neuro-nefrotoxicity; any other G4 toxicity. In case of I dose limiting toxicity (DLT) observed in the first 10 evaluable (eval) pts, the level is considered safe and closed; in case of 2 DLT the accrual of pts is pursued up to 15 eval pts. The MTD is defined as the level in which 3 pts/15 eval develop a DLT (20%). Since 09/93,28 pts with advanced previously untreated STS have been entered in the first 2 levels. Patients characteristics are: 14 males, 14 females, median age 49 (19–66), median PS (0–2); site of origin was extraskeletal in 20, visceral in 8. Measurable/evaluable parameters were present in 25 pts. Overall, 13 pts entered the tirst level: I early PRO, 2 not eval and 10 eval for the MTD definition (JOLT); 15 entered the second level: 2 early PRO, 2 not oval, 4 in progress and 7 eval for the MTD definItion (2DLT). The study is ongoing in order to complete the second level (15 eval pts).