Abstract 1661: Temozolomide suppresses a doxorubicin resistant follicular dendritic cell sarcoma in a patient derived orthotopic xenograft mouse model

Abstract

Abstract Introduction: Follicular dendritic cell sarcoma (FDCS) is a very rare and highly refractory soft tissue sarcoma. The CHOP chemotherapy has been used as systemic therapy for FDCS, which includes cyclophosphamide, doxorubicin (DOX), vincristine, and prednisolone. However, FDCS has poor clinical outcome even though CHOP therapy was administered. A FDCS patient tumor was previously implanted orthotopically in the biceps femoris of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model in our laboratory at AntiCancer Inc. The FDCS patient had resistance to DOX in clinical setting. We previously found the FDCS PDOX model had resistance to DOX as well as clinical settings. In the present study, we evaluated the efficacy of temozolomide (TMZ), trabectedin (TRAB), and pazopanib (PAZ) on the DOX resistant FDCS PDOX model. Methods: The FDCS PDOX mouse model was established and randomized into five groups of eight mice, respectively. Group 1, Control (Ctrl) treated with PBS, i.p.; Group 2, DOX, 2.4 mg/kg, i.p., weekly; Group 3, PAZ, 50 mg/kg, oral gavage, daily; Group 4, TRAB, 0.15 mg/kg, i.v., weekly; Group 5, TMZ, 25 mg/kg, oral gavage, daily. Treatment term was for 2 weeks. Treatment efficacy was evaluated based on tumor volume ratio (tumor volume after treatment relative to tumor volume at the beginning of treatment) and histopathology. Adverse event was evaluated based on body weight ratio. Tumor volume and body weight were assessed 2 times per week. Results: Tumor volume ratio was the Ctrl group: 11.35±4.50, DOX: 8.24±1.87, PAZ: 9.67±4.66, TRAB: 6.97±3.23, TMZ: 4.28±1.41, respectively. TMZ significantly arrested the FDCS PDOX model compared to the control group (p<0.05). PAZ and TRAB did not have significant efficacy compared to the Ctrl group (p=0.93, p=0.41). In H&E-staining, partial necrosis was detected only in PDOX tumors treated with TMZ. There was no significant difference of body weight among all groups. Conclusion: The FDCS PDOX model was resistant to DOX as well as in the clinical settings demonstrating concordance of the FDCS model and clinic. TMZ was the most effective for the FDCS PDOX mouse model established from a patient who failed DOX treatment. There is possibility that TMZ has effective to FDCS patients who has resistant to the first line chemotherapy. Citation Format: Hiromichi Oshiro, Yasunori Tome, Robert M. Hoffman, Kotaro Nishida. Temozolomide suppresses a doxorubicin resistant follicular dendritic cell sarcoma in a patient derived orthotopic xenograft mouse model [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1661.