The Role of Temozolomide-Irinotecan in Doxorubicin- Resistant Cell Lines of Recurrent Ewing’s Sarcoma, in A Patient Derived Orthotopic Xenograft (PDOX) with EWS-ERG Fusion and CDKN2A Loss: What Impact the Combination has in Real Life Practice?

¹Al Bairouni University Cancer Center, department of medical oncology, Damascus University, Damascus, Syria
²Service d’Oncologie, HÔpital Militaire Principal d’Instruction de Tunis, Tunisia 
³Centre Hospitalier Universitaire de Chicas, Alpes du Sud, France
⁴Department of medical Oncology, Al Bairouni University Cancer Center, Damascus, Syria
⁵Department of Orthopedic Surgery, Al Bairouni University Cancer Center, Damascus, Syria
⁶Department of Radiology, Al Bairouni University Cancer Center, Damascus, Syria
⁷Department of Pathology, Al Bairouni University Cancer Center, Damascus, Syria
⁸Department of Pathology, Tishreen Hospital, Damascus, Syria
⁹Department of Cytogenetic, Al Assad Hospital, Damascus, Syria
¹⁰Basma Charity for Pediatric Oncology, Damascus, Syria

Corresponding Author
Maher Salamoon, Al Bairouni University Cancer Center, Damascus University Damascus- Syria, Tel: +96-393-377-1086.
Received Date: August 24, 2020
Published Date: October 08, 2020
Copyright: Maher Salamoon, et al. © 2020
Citation: Salamoon M. (2020). The Role of Temozolomide-Irinotecan in Doxorubicin-Resistant Cell Lines of Recurrent Ewing’s Sarcoma, in A Patient Derived Orthotopic Xenograft (PDOX) with EWS-ERG Fusion and CDKN2A Loss: What Impact the Combination has in Real Life Practice?. Mathews J Cancer Sci. (5)1:21

ABSTRACT

Introduction: A patient-derived orthotopic xenograft (PDOX) nude-mouse model and irrespective of genetic profile can help guiding our treatment in progressive and resistant Ewing Sarcoma (ES) patients progressed after Doxorubicin containing regimens. 
Patients and methods: In our study, the PDOX mice established model with ES were divided into two arms once tumor mass exceeded 60 mm3: (1) untreated control (2) irinotecan plus temozolomide (irinotecan: intra-peritoneal injection; temozolomide: orally, daily for 14 days). A similar study was carried out on patients from whom the graft was taken. We have collected data from 35 patients of ES: diagnosed, treated and progressed after the first line chemotherapy. Those patients received oral temozolomide 100mg/m² on days 1 through 5 plus IV irinotecan 10-20 mg/m²/day on days 1 through 5 and day 8 through 12 (repeated every 3-4 weeks).
Results: Irinotecan plus temozolomide was found to be an effective combination when compared to the untreated control (p = 0.022) in mice model where tumor shrinkage was observed on day 10. To assure these findings, we have conducted in part, a study employing both Temozolomide and irinotecan in patients resistant to Doxorubicin containing regimens and demonstrating EWS-ERG fusion and CDKN2A loss. However, the same protocol was used to the same patient where the graft was taken showing not complete concordance between the lab and real practice. 
Conclusion: PDOX is a good model to test a library of drugs on. It shows to be a promising method in several studies and in ours as well. Studies demonstrated that the combination of temozolomide/irrinotecan is effective in ES patients in progression after Doxorubicin resistance. 

KEYWORDS: Ewing Sarcoma; Xenograft; Progression; ERG; EWS; CDKN2A