Meta-analysis of ifosfamide-based combination chemotherapy in advanced soft tissue sarcoma

BACKGROUND: This meta-analysis examines the role of ifosfamide-based combination chemotherapy in patients with advanced soft tissue sarcoma. Outcomes of interest include overall survival, response rate, adverse effects, and quality of life. METHODS: A systematic review of the literature was searched to identify relevant articles. RESULTS: Three randomized phase III trials were identified comparing combination chemotherapy regimens containing ifosfamide with regimens without ifosfamide. Two randomized trials demonstrated that the addition of ifosfamide to either doxorubicin or to a regimen of doxorubicin and dacarbazine, significantly improved response rates. One randomized trial reported a significant improvement in overall survival for patients receiving doxorubicin and dacarbazine compared to those receiving a combination of doxorubicin, dacarbazine, and ifosfamide (MAID). A meta-analysis of these studies revealed that the addition of ifosfamide to a chemotherapy regimen significantly improves the tumour response rate (RR, 1.52, p=0.009) but does not produce a significant difference in 1-year survival (RR, 0.98, p=0.76). Higher rates of adverse events, particularly grades 3-4 myelosuppression, were observed in patients who received regimens that contained ifosfamide. A higher rate of toxic deaths was reported in two of the three trials, for the ifosfamide containing regimen. Data on quality of life were not reported. CONCLUSION: In patients with metastatic soft tissue sarcoma, the routine addition of ifosfamide to standard first line doxorubicin-containing regimens is not recommended over single agent doxorubicin. However, it may be reasonable to employ such combinations in patients with symptomatic, locally-advanced, or inoperable soft tissue sarcoma where response might render such tumours resectable.