Non-metastatic Ewing's family tumors: High-dose chemotherapy with stem cell rescue in poor responder patients. Preliminary results of the Italian/Scandinavian ISG/SSG III protocol

Abstract

10014 Background: Poor response to induction chemotherapy negatively affects prognosis for Ewing's sarcoma (ES) patients. To improve outcome, high-dose chemotherapy (HDCT) with stem cell rescue was added to conventional chemotherapy in patients poor responders after induction treatment. Methods: Non-metastatic ES patients aged <= 40 years were eligible. All patients received VAC (vincristin 2 mg-doxorubicin 80 mg/m2-cyclofosfamide 1,200 mg/m2) weeks 0 and 6, IVAc (ifosfamide 9g/m2-vincristin 2 mg-actinomycin 2 mg) week 3 and IE (ifosfamide 9g/m2-etoposide 450 mg/m2) week 9 as induction therapy. Poor response was histologically defined as persistence of microfoci of viable tumor cells and radiologically as persistence of soft tissue mass. As maintenance treatment good responders (GR) received three cycles of VAC-IVAc-IE. Poor responders (PR) received VAC (weeks 13,19), IE (week 22), CE (mobilizing cycle, cyclophoshamide 4g/m2, etoposide 600 mg/m2, week 16) and HDCT with BuMel (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2 with stem cell support week 25). Results: Starting from 1999, 296 patients were enrolled with a median age of 15 years (3–40). 54 % of the tumors were located to the extremities and 46% in the axial skeleton. 274 patients underwent local treatment: surgery in 222 (81%) patients (with post operative Rxt in 70), RxT alone in 52 (19%). 10 patients progressed during treatment. No toxic deaths were recorded. Response evalutation was available for 262 patients: 135 (52%) were PR. 116 of them completed protocol treatment and 19 did not receive HDCT (5 poor harvest, 5 medical contraindication, 9 refusal).With a median follow-up of 37 months (1–89) 5-year overall and event-free survival were 74 % and 65.5% respectively. 5-year event-free survival was 71% (95% CI 62–81%) for GR, 68% (95% CI 58–78%) for PR treated with HDCT and 35% (95% CI 10–60%) for PR who did not receive HDCT. Conclusions: The preliminary survival data show for PR similar outcome as for GR. The treatment including HDCT is feasible with no toxic death recorded. Longer follow-up will confirm its efficacy. No significant financial relationships to disclose.