The role of chemotherapy for metastatic, relapsed and refractory osteosarcoma.

UNLABELLED Despite a large number of publications on outcomes of second-line chemotherapy for osteosarcoma, there is little consensus on efficacy of the therapy. OBJECTIVE Our objective was to systematically categorize published evidence for chemotherapy for metastatic, relapsed and refractory osteosarcoma in order to provide an updated and comprehensive analysis of the clinical outcomes. METHODS We performed a search of PubMed and EMBASE to identify published articles reporting on validated clinical outcomes measures (the rate of complete response [CR] and partial response [PR], the rate of stable disease [SD] and progressive disease [PD] and the 5-year overall survival) after chemotherapy in patients with metastatic, relapsed and refractory osteosarcoma. A total of 20 articles were identified and stratified by different regimens. Finally, six regimens that have at least two drugs were reviewed. Weighted averages of each outcome were computed. RESULTS The weighted average overall response rate (CR + PR) for the combination of ifosfamide, etoposide and high-dose methotrexate therapy was 62 %, and the tumor control rate (CR + PR + SD) was 92.3 %; the highest of all six regimens. The weighted average overall response rate and tumor control rate of ifosfamide-etoposide therapy (41.7 and 77.9 %, respectively) were the highest of the two-drug regimens. Weighted average overall response rate and tumor control rate for the remaining regimens were 20.5 and 56.8 %, respectively, for cyclophosphamide-etoposide; 30.0 and 73.5 % for ifosfamide, carboplatin, and etoposide; 12.0 and 40.0 % for cyclophosphamide-topotecan; and 14.5 and 36.4 % for gemcitabine-docetaxel. CONCLUSION A chemotherapy regimen comprising both a cell cycle-specific drug and a cell cycle-nonspecific drug could increase response rates. The combination of ifosfamide and etoposide therapy is our first choice in two-drug regimens. Regarding three-drug regimens, adding a cell cycle-specific drug to ifosfamide-etoposide therapy may result in a better response rate than adding a cell cycle-nonspecific drug, or any other two-drug regimens in current studies. Hence, we recommend the use of second-line chemotherapy based on the combination ifosfamide-etoposide regimen in patients with metastatic, relapsed and refractory osteosarcoma.