Regorafenib regressed a doxorubicin-resistant Ewing's sarcoma in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

Abstract

PURPOSE:

Ewing's sarcoma (ES) is a rare and recalcitrant disease which is in need of a development of a novel effective therapy. The aim of this study was to investigate the efficacy of regorafenib on an ES tumor in a patient-derived orthotopic xenograft (PDOX) model.

METHODS:

The ES PDOX models were established orthotopically in the right chest wall of nude mice to match the site of the tumor in the donor patient. The ES PDOX models were randomized into three groups (G) when the tumor volume reached 75 mm3: G1: untreated control; G2: doxorubicin (DOX) (i.p., 3 mg/kg, weekly, 2 weeks); G3: regorafenib (REG) (p.o., 30 mg/kg, daily, 2 weeks). Tumor volume and body weight were measured twice a week. All mice were sacrificed on day 15.

RESULTS:

DOX was ineffective compared to the control group (P = 0.229). REG regressed the tumor size (P < 0.001 and P < 0.001, relative to control and DOX, respectively).

CONCLUSIONS:

Our findings suggest that REG has clinical potential for ES patients whose tumors respond to REG in a PDOX model.

• Authors: Kentaro Miyake, Tasuku Kiyuna, Kei Kawaguchi, Takashi Higuchi, Hiromichi Oshiro, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Yunfeng Li, Scott D Nelson, Takashi Murakami, Yukihiko Hiroshima, Ryusei Matsuyama, Michael Bouvet, Sant P Chawla, Shree Ram Singh, Itaru Endo, Robert M Hoffman
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 83 Issue 5 Pg. 809-815 (05 2019) ISSN: 1432-0843 [Electronic] Germany
• PMID: 30758647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Pyridines
• regorafenib
• Doxorubicin

Topics

• Animals
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Body Weight (drug effects)
• Bone Neoplasms (drug therapy, pathology)
• Doxorubicin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Mice, Nude
• Phenylurea Compounds (administration & dosage, therapeutic use)
• Pyridines (administration & dosage, therapeutic use)
• Sarcoma, Ewing (drug therapy, pathology)
• Treatment Outcome
• Tumor Burden (drug effects)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays