Adjuvant and neoadjuvant chemotherapy (NAC) with ifosfamide (IFO) and doxorubicin hydrochloride (ADM) for high-grade soft tissue sarcomas (STS) in the extremities: Japan Clinical Oncology Group study JCOG030404.

Abstract

10078 Background: STS are rare malignant tumors and relatively resistant against chemotherapy. The efficacy of systemic adjuvant chemotherapy for STS is still controversial and only a few prospective trials of NAC for STS in the extremities have been reported. We therefore carried out the multicenter phase II study of NAC for patients with STS in the extremities. Methods: Patients with operable, FNCLCC grade 2/3 non-round cell STS in the extremities, Stage III (T2bN0M0, AJCC 6th edition), ECOG performance status 0-1, and age 20-70 were eligible. The patients were initially treated with NAC consisted of ADM 60mg/m2 and IFO 10g/m2 for 3 courses with 3-week interval. After the completion of tumor resection, additional 2 courses of the same regimen as NAC were carried out. The primary endpoint was 2-year progression-free survival rate (PFS). Results: A total of 72 patients were enrolled and 70 patients were eligible. The median age of the patients was 49 years (21-66), 53% were male. The major pathological subtypes were synovial sarcoma 20, malignant fibrous histiocytoma 17 and leiomyosarcoma 11 patients. The protocol treatments were completed in 74 % of the eligible cases. Seventy patients underwent surgery as protocol treatment. Wide margin was achieved in 61 patients, whereas marginal margin and intralesional margin were in 8 and 1 patients, respectively. With median follow-up of 3.6-year for eligible cases, 2-year and 4-year PFS were 75.7% and 65.3%, respectively. Overall survival rates for 2-year and 4-year were 91.4% and 81.8%, respectively. There was no treatment related death. Grade 3 or 4 hematologic toxicities (leucopenia and neutropenia) were observed in most of the patients and the most frequent non-hematologic toxicities were nausea and appetite loss. Conclusions: Although the toxicities of the regimen were significant, NAC followed by post-operative chemotherapy using ADM and IFO was well tolerable. The outcome of the trial for the patients with operable, high-grade STS in the extremities was far better than expected, and this regimen is promising for further investigation by phase III trials.