A novel anionic-phosphate-platinum complex effectively targets an undifferentiated pleomorphic sarcoma better than cisplatinum and doxorubicin in a patient-derived orthotopic xenograft (PDOX)

// Kentaro Igarashi 1, 2, 3 , Kei Kawaguchi 1, 2 , Takashi Murakami 1, 2 , Tasuku Kiyuna 1, 2 , Kentaro Miyake 1, 2 , Norio Yamamoto 3 , Katsuhiro Hayashi 3 , Hiroaki Kimura 3 , Scott D. Nelson 4 , Sarah M. Dry 4 , Yunfeng Li 4 , Arun S. Singh 5 , Shinji Miwa 3 , Akira Odani 6 , Fritz C. Eilber 7 , Hiroyuki Tsuchiya 3 and Robert M. Hoffman 1, 2 1 AntiCancer, Inc., San Diego, California, USA 2 Department of Surgery, University of California, San Diego, California, USA 3 Department of Orthopaedic Surgery, Kanazawa University, Kanazawa, Japan 4 Department of Pathology, University of California, Los Angeles, California, USA 5 Division of Hematology-Oncology, University of California, Los Angeles, California, USA 6 Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan 7 Division of Surgical Oncology, University of California, Los Angeles, California, USA Correspondence to: Robert M. Hoffman, email: all@anticancer.com Fritz C. Eilber, email: fceilber@mednet.ucla.edu Hiroyuki Tsuchiya, email: tsuchi@med.kanazawa-u.ac.jp Keywords: platinum complex, 3Pt, undifferentiated pleomorphic sarcoma, PDOX, efficacy Received: April 25, 2017 Accepted: May 12, 2017 Published: June 28, 2017 ABSTRACT A patient high-grade undifferentiated pleomorphic soft-tissue sarcoma (UPS) from a striated muscle was previously orthotopically implanted in the right biceps femoris muscle of nude mice to establish a patient-derived orthotopic xenograft (PDOX) nude-mouse model. In the present study, two weeks after orthotopic transplantation of the UPS, mice were treated intraperitoneally with cisplatinum (CDDP), doxorubicin (DOX) or a novel anionic-phosphate-platinum compound 3Pt. Treatments were repeated weekly for a total of 3 times. Six weeks after transplantation, all mice were sacrificed and evaluated. After two weeks treatment, tumor sizes were as follows: control (G1): 2208.3 mm 3 ; CDDP (G2): 841.8±3 mm 3 , p=0.0001; DOX (G3): 693.1±3 mm 3 , p=6.56E-7; 3Pt (G4): 333.7±1 mm 3 , p=4.8E-8. 3Pt showed significantly more efficacy compared to other therapy drugs tested: CDDP (p=0.0002), DOX (p=0.001). There were no animal deaths in any of the four groups. The present results suggest 3Pt is a promising new candidate for UPS since it was demonstrated to be effective in a PDOX model.