(P 80) OPTIMIZING DOSE OF MAP THERAPY FOR CHILDREN, YOUNG ADULTS AND ADULTS WITH OSTEOSARCOMA; A SINGLE-CENTRE RETROSPECTIVE ANALYSIS

Objective: MAP (Methotrexate: MTX, Adriamycin: ADR, Cisplatin: CDDP) therapy is a standard chemotherapy for patients with osteosarcoma across all ages. Although adult patients are more toxic to anticancer therapy than pediatric patients, and thus dose intensities cannot be maintained, the dose intensity that is appropriate for each age group is not clear. We performed a retrospective analysis of patients with osteosarcoma to investigate whether the dose reduction of MAP therapy affects the efficacy and feasibility in patients with osteosarcoma in each age group.

Methods: We performed a single-center retrospective chart review analysis. Patients who were histologically diagnosed with osteosarcoma and received MAP therapy from January 1, 2014 to December 31, 2021 were included. Patients with recurrence, those who previously received MAP therapy at other hospitals, and those who received other agents such as ifosfamide or radiotherapy were excluded. We classified the patients as pediatric (PED, 0-19 years old), young adults (YA, 20-39 years old), and older adults (OA, 40 years old and older). Patients were classified according to the doses per cycle (DPC) they were scheduled to receive and the dose intensity (DI) they received for each agent. To calculate DI, we used DI-200, which is the total amount of the agent a patient received by day 200 of chemotherapy. We evaluated the relapse-free survival (RFS), therapy-complete rate (TCR), and serious adverse events in each age group, DPC, and DI-200. For the DI-200 analysis, only patients who survived to day 200 of chemotherapy without disease progression or relapse were included. This study was approved by our institutional ethical review board.

Results: During the study period, 78 osteosarcoma patients received MAP therapy in our hospital. Of these, 24 patients were excluded (7 relapsed, 4 previously received MAP therapy in other hospitals, 13 received other agents), and the remaining 54 patients were analyzed. There were 24 PED patients, 19 YA patients, and 11 OA patients. Significant differences were observed in the proportion of patients with a primary site other than extremity (PED 9 %, YA 52 %, OA 81 %, p< 0.01), the median number of preoperative chemotherapy cycles (PED 6, YA 5, OA 0, p< 0.01), and metastases at diagnosis (PED 29 %, YA 15 %, OA 18 %, p< 0.01). The median DPC of MTX was 12 g/m2 in PED, 10 g/m2 in YA, and 8 g/m2 in OA patients, respectively. The median DPC of CDDP was 120 mg/m2 in PED and YA, and 80 mg/m2 in OA patients, respectively. All patients except the one patient received ADR 60 mg/m2 per cycle. The median DI-200 was 80 g/m2 for MTX, 330 mg/m2 for ADR, and 480 mg/m2 for CDDP, respectively. The median MTX DI-200 was 96 g/m2 in PED, 72 g/m2 in YA, and 42.3 g/m2 in OA (p < 0.01). The median CDDP DI-200 was 480 mg/m2 in PED, 460 mg/m2 in YA, and 370 mg/m2 in OA (p < 0.01). There was no statistical significance in RFS across age groups, DPC and DI-200 of each agent. We compared RFS stratified by DPC and DI-200 in each age group, and the higher dose group in DPC and DI-200 did not show superiority. On multivariate analysis of RFS, neither the age group, DPC and DI-200 showed statistical significance. For TCR, the OA patient group was statistically lower. Renal dysfunction and delayed elimination of MTX were identified as the main reasons for the discontinuation of MAP therapy. There was no statistical significance for serious adverse events when compared by age group and DPC.

Conclusion: The optimal dose of MAP therapy may differ among age groups. A prospective study in all age groups is needed to determine the optimal dose of MAP therapy.