The Latin American Group of Osteosarcoma Treatment has just published in Cancer the results of a randomized trial, evaluation the addition of a metronomic maintenance for patients with a resectable, non metastatic osteosarcoma. The first author of the paper, Andreza A. Senerchia, is one of our MGHI member. Although, at last follow-up, EFS with MAP plus MC maintenance is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities, one shall not conclude that a metronomic maintenance is useless in OS. Different maintenances not relying on MTX might be used, and shall not start during the MTD chemotherapy.

BACKGROUND Metronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an anti-tumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high-grade operable osteosarcomas (OSTs) of the extremities was investigated.

METHODS Patients with high-grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event-free survival (EFS) from randomization.

RESULTS There were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP-MC group and the MAP-alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS.

CONCLUSIONS According to the current follow-up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high-grade, resectable OSTs of the extremities.