Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcoma

Leiomyosarcomas (LMS) are rare tumors with poor prognosis owing to the high rate of recurrent and metastatic disease. The combination of doxorubicin (Adriamycin) plus ifosfamide and mesna (AIM) results in moderate response rates of 10%-30%. The aim of this study was to assess the efficacy of the AIM regimen along with multimodality treatment including surgery and radiotherapy in patients with LMS. The clinicopathologic characteristics and outcomes of 51 patients with recurrent or metastatic LMS diagnosed between 2000 and 2014 who received the AIM regimen were analyzed retrospectively. Treatment consisted of ifosfamide 2500mg/m² on days 1-3 (with mesna 2500mg/m² days 1-3, 4-hour i.v. infusion), and doxorubicin 60mg/m² on day 1 (2-hour i.v. infusion), which was repeated every 21 days. The mean age of the patients at diagnosis was 48.9 ± 11.2 years. A total of 42 patients were females (82.4%). The primary tumor site was the uterus in 30 (58.8%) patients. The most common metastatic sites were lung and liver. The median follow-up was 27.9 months (min: 4.3 max: 164.8). The median progression-free survival was 6.7 months (95% CI: 4.1-9.2). The median overall survival (OS) was 24.6 months (95% CI: 16.2-33.0). The overall response rate was 12% (6/51 pts). Response rates were higher in patients with uterine LMS (17%) compared with those with nonuterine LMS (5%); however, the OS times were similar. Surgical intervention for local or distant recurrence was associated with improved median OS (41 vs 16.6 months, P < 0.001). Myelosuppression was the major toxicity of this combination. In our study, the AIM regimen was effective in patients with LMS. Resection of local or distant recurrence was found to improve survival in our study.