The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a
doxorubicin-resistant metastatic
Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line
chemotherapy of the patient. Our previous study showed that
cyclin-dependent kinase 4/6 (CDK4/6) and
insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the
Ewing's sarcoma PDOX, but not
doxorubicin, similar to the patient's resistance to
doxorubicin. The results of the previous PDOX study were successfully used for second-line
therapy of the patiend. In the present study, the PDOX mice established with the
Ewing's sarcoma in the right chest wall were randomized into 5 groups when the
tumor volume reached 60 mm3: untreated control;
gemcitabine combined with
docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks);
irinotecan combined with
temozolomide (
irinotecan: i.p. injection;
temozolomide:
oral administration, daily, for 2 weeks);
pazopanib (
oral administration, daily, for 2 weeks);
yondelis (
intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15.
Body weight and
tumor volume were assessed 2 times per week.
Tumor weight was measured after sacrifice.
Irinotecan combined with
temozolomide was the most effective regimen compared to the untreated control group (p=0.022).
Gemcitabine combined with
docetaxel was also effective (p=0.026).
Pazopanib and
yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line
therapy of the patient.