Metronomic chemotherapy (MC) does not improve the event-free survival (EFS) of patients with non-metastatic osteosarcoma, according to a study published in Cancer.1

The standard chemotherapy for patients with high-grade, operable osteosarcoma is a combination of methotrexate, adriamycin, and cisplatin (MAP). For the present study, researchers hypothesized that adding a MC regimen, which is given at a low dose without large treatment-breaks, would improve EFS in this patient population.

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This prospective, randomized study ( Identifier: NCT02273583) compared EFS in 2 treatment groups: MAP + MC, MAP alone. The MC component included cyclophosphamide and methotrexate.

Of 422 total registered participants, 139 were randomized to MAP + MC, while 157 were randomized to MAP alone. All randomized patients were included in the analysis, though 49 patients in the MAP + MC group did not initiate MC for varying reasons.

The mean EFS time was 51.58 months in the MAP-MC group and 58.81 months in the MAP group. The mean overall survival times were 65.82 months and 66.16 months for MAP + MC and MAP, respectively.

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Three patients died from treatment-related toxicity in the MAP-MC group; 4 died from toxicity in the MAP group.

The authors conclude that this MC regimen should not be used in non-metastatic osteosarcoma. The treatment may, however, be useful in metastatic disease settings.


  1. Senerchia AA, Macedo CR, Ferman S, et al. Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high-grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment. Cancer. 2016 Nov 7. doi: 10.1002/cncr.30411 [Epub ahead of print]