Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: Results of the Italian randomized cooperative trial

Purpose: Adjuvant chemotherapy for soft tissue sarcoma is controversial bec ause previous trials reported conflicting results. The present study wets d esigned with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. Patients and Methods: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter greater than or equal to 5 cm or any size recurrent turner) in extremities or girdles were eligible. Stra tification was by primary versus recurrent tumors and by tumor diameter gre ater than or equal to 10 cm versus less than 10 cm. One hundred four patien ts were randomized, 51 to the control group and 53 to the treatment group ( five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-sti mulating factor). Results: After a median follow-up of 59 months, 60 patients had relapsed an d 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P = .04); and the medi an overall survival (QS) was 75 months for treated and 46 months for untrea ted patients (P = .03). For OS, the absolute benefit deriving from chemothe rapy was 13% at 2 years and increased to 19% at 4 years (P = .04). Conclusion: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a m edian follow-up of 59 months. Therefore, our data favor an intensified trea tment in similar cases. Although cure is still difficult to achieve, a sign ificant delay in death is worthwhile, also considering the short duration o f treatment and the absence of toxic deaths. J Clin Oncol 19:1238-1247. (C) 2001 by American Society of Clinical Oncology.