What is the role of chemotherapy in the treatment of osteosarcoma?

Updated: Jul 01, 2020
  • Author: Charles T Mehlman, DO, MPH; Chief Editor: Omohodion (Odion) Binitie, MD  more...
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So-called neoadjuvant (preoperative) chemotherapy has been found not only to facilitate subsequent surgical removal by causing tumor shrinkage but also to provide oncologists with an important risk parameter. Patients in whom there has been a good histopathologic response to neoadjuvant chemotherapy (>95% tumor cell kill or necrosis) have a better prognosis than those whose tumors do not respond as favorably. Thus, future chemotherapy trials will incorporate adjuvant tumor cell kill to provide risk-adapted treatment regimens.

Patients receiving methotrexate should not be given folate supplementation or trimethoprim-sulfamethoxazole, both of which interfere with the effects of methotrexate. Otherwise, the patient's diet is not restricted.

Xiao et al conducted a literary review intended to shed light on the clinical outcomes of various chemotherapy regimens in the treatment of metastatic, relapsed, and refractory osteosarcoma. [37] They concluded that a chemotherapy regimen comprising both a cell cycle–specific drug and a cell cycle–nonspecific drug could increase response rates.

Xiao et al found that for 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 regimen among those in their study. [37] For patients with metastatic, relapsed, and refractory osteosarcoma, they recommended the use of second-line chemotherapy that is based on the combined ifosfamide-etoposide regimen.

In the EURAMOS-1 trial, a randomized controlled study designed to investigate whether intensified postoperative chemotherapy for patients with newly diagnosed high-grade osteosarcoma whose tumor responded poorly to preoperative chemotherapy improved event-free survival, Marina et al compared a postoperative MAP (cisplatin, doxorubicin, methotrexate) regimen (n = 310) with a regimen in which ifosfamide and etoposide were added to MAP (MAPIE; n = 308). [38]  The primary outcome measure was event-free survival in the intent-to-treat population. 

At a median follow-up of 62.1 months, 307 event-free survival events were reported (153 in the MAP group vs 154 in the MAPIE group), and there were 193 deaths (101 in the MAP group vs 92 in the MAPIE group). [38] Event-free survival did not differ between treatment groups. The most common grade 3-4 adverse events were neutropenia, thrombocytopenia, and febrile neutropenia without documented infection. MAPIE was associated with more frequent grade 4 nonhematologic toxicity than MAP was. The study results results did not support the addition of ifosfamide and etoposide to postoperative chemotherapy in this setting.

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