Preliminary Safety And Outcome Report Of The Metronomic Therapy From The Latin American Osteosarcoma Treatment Protocol 2006.

10032 Background: Based on results from leukemia maintenance therapy, anti-angiogenic approaches have been indicated as alternatives for solid tumors. In this rationale, metronomic therapy (MT) emerged as a low toxicity, low cost, oral treatment aiming to increase survival. Methods: 429 high-grade extremity osteosarcoma patients were enrolled in this study. Standard therapy consists of cysplatin, doxorubicin and HDMTX. Non-metastatic patients (NMP) are randomized at the end of MTD treatment (week 31) for no treatment (arm A) or MT until week 104 (arm B). All metastatic patients (MP) are assigned to MT concomitant with MTD treatment until week 104. 92 patients (26 MP and 66 NMP) were excluded as they did not receive MT or were not randomized. There is data from 242 patients in the group database. 91 MP and 72 arm B NMP received MT: CTX 25mg/m2/day everyday and MTX 3mg/m2/day twice a week. Dosage modifications were allowed to keep WBC count <3500/mm3 or due to grade 3/4 toxicities. Adherence to treatment was self-reported and recorded on patient charts. In this study, one cycle of MT was 28 days. Circulating and tumoral THBS1, VEGFA, PDGFC, FLT1, KBR, CXCL12 and CXCR4 protein and gene expression are being investigated to evaluate angiogenic activity and identify possible angiogenic markers. Results: The main toxicity found during MT alone was anemia grade I in 27% of the cycles. Neutropenia grades 3/4 was found on 3.5% of the cycles. In around 72% of the cycles, a dosage increase was needed due to high WBC counts. 88% of arm B NMP remain alive with median follow-up time of 23 months (versus 89% of patients not randomized to MT). Relapse was seen on 16% of the cases (versus 18%). 79% of MP remain alive with median follow-up time of 23 months (versus 57% of patients that did not receive MT). Conclusions: MT is well tolerated with no grade 3/4 non-hematological toxicities when used alone and did not increase toxicities if used concomitantly with MTD chemotherapy. The number of patients and short follow-up period restricts the outcome analysis but it seems that metronomic therapy may play an important role on avoiding disease progression for metastatic patients while its role on avoiding relapse needs further evaluation.