Treatment of children with metastatic soft tissue sarcoma with oral maintenance compared to high dose chemotherapy: Report of the HD CWS-96 trial

Purpose. We prospectively Studied the efficacy of high dose therapy (HDT) versus an oral maintenance treatment (OMT) in patients with stage IV soft tissue sarcorna (STS). Patients and Methods. Both groups were pretreated with the CEVAIE combination consisting of carboplatin, etoposide, vincristine, actinomycin D, ifosfamide, and epirubicin. HDT consisted of a tandem cycle of thiotepa (600 mg/m(2)) plus cyclophosphamide (4,500 mg/m2) and melphalan (120 mg/m(2)) Plus etoposide (1,800 mg/m(2)). This treatment was compared with OMT, consisting of four cycles trofosfamide (10 days 2 x 75 mg/m(2)/clay) plus etoposide 0 0 days 2 x 25 mg/m(2)/day), and 4 cycles trofosfamide (10 days 2 x 75 mg/m(2)/day) plus idarubicin (10 days 4 x 5 mg/m(2)). Eligibility criteria were: diagnosis confirmed by reference pathology, primary stage IV, below 22 years of age, and having completed the study therapy. Results. From 96 patients 45 were treated with HDT and 51 with OMT. The main risk parameters were equally distributed in both arms. After a median follow-up of 57.4 months, 11/45 (24.4%) patients in the HDT-arm and 26/51 (57.8%) patients in OMT-arm were alive. Kaplan-Meier analysis demonstrated an overall Survival for the whole group Of 0.27 (OMT group: 0.52, HDT group 0.27, log rank P=0.03). The proportional hazard analysis for patients with rhabdomyosarcoma (RMS) or "RMS-like" turners (77.1% of all patients) demonstrated an independent benefit of OMT on outcome. Conclusion. Oral maintenance therapy seems to be a promising option for patients with RMS-like stage IV tumors.