Gemcitabine combined with docetaxel precisely regressed a recurrent leiomyosarcoma peritoneal metastasis in a patient-derived orthotopic xenograft (PDOX) model
2019
Miyake, Kentaro | Kiyuna, Tasuku | Miyake, Masuyo | Kawaguchi, Kei | Zhang, Zhiying | Wangsiricharoen, Sintawat | Razmjooei, Sahar | Oshiro, Hiromichi | Higuchi, Takashi | Li, Yunfeng | Nelson, Scott D. | Murakami, Takashi | Hiroshima, Yukihiko | Kumamoto, Takafumi | Matsuyama, Ryusei | Bouvet, Michael | Singh, Shree Ram | Chawla, Sant P. | Endo, Itaru | Hoffman, Robert M.
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.
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