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

Biochem Biophys Res Commun. 2019 Feb 19;509(4):1041-1046. doi: 10.1016/j.bbrc.2019.01.046. Epub 2019 Jan 16.

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.

Keywords: Docetaxel; Gemcitabine; Leiomyosarcoma; Nude mice; PDOX; Patient-derived orthotopic xenograft.

MeSH terms

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

Substances

  • Deoxycytidine
  • Docetaxel
  • gemcitabine