Chemotherapy in Nonmetastatic Osteosarcoma: Recent Advances and Implications for Developing Countries

Purpose: Osteosarcoma (OS) is a relatively chemosensitive primary bone tumor, with the peak age of onset occurring in late childhood and early adolescence. The treatment paradigm of nonmetastatic OS has typically been multimodality therapy, including neoadjuvant and adjuvant chemotherapy with definitive surgery. Over the years, various permutations and combinations of chemotherapeutic agents have been used. However, the majority of recent trials have still used high-dose methotrexate as the backbone, with cisplatin and doxorubicin (MAP). In the last decade, various strategies targeted to improving outcomes in OS have included the addition of a fourth drug to the three-drug MAP regimen, changing therapy according to histopathologic response and the addition of immunotherapies. Through this review, we sought to underscore a few pertinent issues related to chemotherapy in nonmetastatic OS, with special reference to challenges confronted in Indian settings. Methods: We reviewed the literature, focusing on studies comparing high-dose methotrexate and non–high-dose methotrexate–containing regimens. In addition, this review focuses on non–methotrexate-containing triple-drug therapy. Results: Although a high-dose methotrexate regimen has become standard of care in developed countries, there are few data to suggest that it is superior to a non–high-dose methotrexate regimen. Conclusion: Developing countries with lack of infrastructure and logistics for high-dose methotrexate might resort to non–high-dose methotrexate–containing regimens with a simultaneous focus on early detection, decreasing abandonment, multidisciplinary clinics, improved surgery, and meticulous pathologic evaluations