Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model.

Abstract

There are no effective treatments for leiomyosarcoma (LMS) spreading intraabdominally. The aim of this study was to develop precision chemotherapy for recurrent peritoneal LMS metastases in a patient-derived orthotopic xenograft (PDOX) model. The LMS PDOX models were established orthotopically on the dome of the bladder of nude mice. The LMS PDOX models were randomized into 6 groups when the tumor volume reached 80 mm3: G1: untreated control; G2: doxorubicin (DOX) (DOX: i.p., 3 mg/kg, weekly, 3 weeks); G3: DOX combined with olaratumab (OLA) (DOX: i.p., 3 mg/kg, weekly, 3 weeks; OLA: i.p., 40 mg/kg, 3 times/week, 3 weeks); G4: gemcitabine (GEM) combined with docetaxel (DOC) (GEM: i.p., 100  mg/kg, weekly, 3 weeks; DOC: i.p., 20  mg/kg, weekly, 3 weeks); G5: pazopanib (PAZ) (PAZ: p.o., 100  mg/kg, daily, 3 weeks); G6: palbociclib (PAL) (PAL: p.o., 100  mg/kg, daily, 3 weeks). All mice were sacrificed on day 22. Body weight was assessed twice a week. Tumor volume was measured on day 0 and day 22. Although all regimens had a significant efficacy compared to the untreated group (P < 0.001), only GEM combined with DOC regressed the tumor significantly (P < 0.001), suggesting GEM combined with DOC has clinical potential for this LMS patient.

• Authors: Kentaro Miyake, Tasuku Kiyuna, Masuyo Miyake, Kei Kawaguchi, Zhiying Zhang, Sintawat Wangsiricharoen, Sahar Razmjooei, Hiromichi Oshiro, Takashi Higuchi, Yunfeng Li, Scott D Nelson, Takashi Murakami, Yukihiko Hiroshima, Takafumi Kumamoto, Ryusei Matsuyama, Michael Bouvet, Shree Ram Singh, Sant P Chawla, Itaru Endo, Robert M Hoffman
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 509 Issue 4 Pg. 1041-1046 (02 19 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30660363 (Publication Type: Journal Article)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Deoxycytidine
• Docetaxel
• Gemcitabine

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Deoxycytidine (analogs & derivatives, therapeutic use)
• Docetaxel (therapeutic use)
• Heterografts
• Humans
• Leiomyosarcoma (drug therapy, pathology)
• Mice
• Mice, Nude
• Neoplasm Metastasis (prevention & control)
• Peritoneal Neoplasms (drug therapy, pathology)
• Recurrence
• Salvage Therapy (methods)
• Treatment Outcome
• Tumor Burden (drug effects)
• Gemcitabine