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

Author:

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
Author Address

AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA; Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan., AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA., AntiCancer Inc, San Diego, CA, USA., Dept. of Pathology, University of California, Los Angeles, CA, USA., Basic Research Laboratory, National Cancer Institute, Frederick, MD, USA. Electronic address: singhshr@mail.nih.gov., Sarcoma Oncology Center, 2811 Wilshire Blvd, Suite 414, Santa Monica, CA, 90403, USA., Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan. Electronic address: endoit@med.yokohama-cu.ac.jp., AntiCancer Inc, San Diego, CA, USA; Department of Surgery, University of California, San Diego, CA, USA. Electronic address: all@anticancer.com.,

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. Copyright © 2019. Published by Elsevier Inc.

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