Background/Aim: We have previously developed a novel bone-targeting platinum compound, 3Pt, and showed that it has strong inhibitory activity against osteosarcoma cells and orthotopic cell-line xenograft mouse models. In the present report, we compared the efficacy of 3Pt to cisplatinum (CDDP) in a CDDP-resistant relapsed osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. Patients and Methods: The tumor of a patient with osteosarcoma of the distal femur was treated with CDDP-based chemotherapy followed by surgery. The surgical specimen was used to establish a PDOX model. An osteosarcoma cell line was also established from the original patient tumor. Osteosarcoma cell viability was assessed with the WST-8 assay and the IC50 values were calculated. The PDOX models were randomized into three groups: untreated control, CDDP-treated group, and 3Pt-treated group. Tumor size and body weight were measured twice a week. Results: 3Pt had a strong concentration-dependent cytocidal effect in vitro. The IC 50 value of 3Pt was significantly lower than that of CDDP. On day 14 of the treatment, 3Pt caused a significantly greater tumor growth inhibition compared to the untreated control and CDDP-treated mice. Conclusion: 3Pt is a promising clinical candidate for the treatment of recalcitrant osteosarcoma. Osteosarcoma is a rare and highly malignant mesenchymal bone tumor. The primary tumor is pathologically characterized by the formation of immature bone or osteoid. A bimodal distribution of osteosarcoma occurence has been reported, with a first peak in adolescence and a second peak in older age (1). Patients with osteosarcoma treated with chemotherapy and surgery have approximately a 70% 5-year survival rate (2-4). First-line chemotherapy for osteosarcoma includes highdose methotrexate (MTX), cisplatinum (CDDP), doxorubicin, (DCX) and ifosfamide (IFS) (5-9). However, dose escalation of these drugs has not been effective for recalcitrant osteosarcoma (6), with 5-year overall survival rates being less than 20% (6-9). We have previously developed a novel platinum complex 3Pt ([Pt(Pt(1R,2R-diaminocyclohexane)(myo-inositol-1,2,3, 4,5,6-hexakisphosphate))2]), which comprises anionic phosphate moieties (10). The cytotoxic potency of 3Pt was higher than that of CDDP in all osteosarcoma cell lines tested. 3Pt was also effective in CDDP-resistant cells (10). Mice treated with 3Pt showed no renal cell injury compared 217 This article is freely accessible online.