Treatment of patients with high-risk axial and pelvic Ewing’s sarcoma (ES). A single-institution experience
Roman I. Pimenov1, Igor S. Dolgopolov1, Vasilii K. Boyarshinov1, Natalia S. Subbotina1, Igor V. Visochin1, Stuart Siegiel2, George L. Mentkevich1
1Institute of Pediatric Oncology and Hematology, Bone Marrow Transplantation Department, Moscow, Russia; 2CHLA, Los-Angeles, USA
Roman I. Pimenov, 24, Kashirskoye shosse, 115476, Moscow, Russia, Phone: +7 (903) 1991909
E-mail: onco@ list.ru
This study was initiated in an attempt to improve DFS rates in patients (pts) with high-risk axial and pelvic ES by using autoPBSCT. From January 1997 to December 2007 35 pts (M/F–15/21) with high-risk ES (localized 25 pts; metastatic 10 pts (lungs-only: 2, combined or other sites: 8) received HDCT with autologous transplantation. The median primary tumor volume was 739 cm3. CT consisted of 5 courses: numbers 1, 3, and 5 included cyclophosphamide 2100 mg/m2 day on days 1 and 2, doxorubicin 37.5 mg/m2 as a 24-hour infusion on days 1 and 2, and vincristine 1.5 mg/m2 on days 1, 8, and 15. Cycles 2 and 4 consisted of ifosfamide 2400 mg/m2/day on days 1–5 and VP-16 100 mg/m2/day on days 1–5. No G-CSF was given routinely between cycles. RT was given after the fifth cycle of CT at a median dose of 52 Gy (range, 50–56). Patients with lung involvement received lung irradiation after the second cycle of CT at a dose of 10.8-12 Gy. All pts received busulfan 16 mg/kg, melphalan 140 mg/m2-based HDCT (n=9); with the addition of thiotepa (TT) 600-900 mg/m2 (n=11) or VP16 1400 mg/m2 (n=15), followed by autologous stem cell recovery (6.4 (1.9–25.3) x 106 CD34+ cells/kg). The median number of days to WBC>1.0x109/l, Plt>20, and 50x109/l was 10 (8–14), 16 (0–52) and 28 (11–66) days, respectively. TRM was 6% (2 pts out of 35). Six pts relapsed. DFS at 5 yrs was 50% in metastatic pts vs 88% in pts with localized tumor (p>0.05). EFS and DFS were 69% and 75% with a median follow-up of 103 and 112 months, respectively. DFS in the TT, VP16, and BuMel groups was 83%, 67%, and 79%, respectively (p<0.05).
We conclude that pts with high-risk ES may benefit from BuMel-based regimens, and that an addition of any drug to BuMel regimen increases toxicity with no influence on DFS.
Ewing’s sarcoma, high-dose chemotherapy, autologous bone marrow transplantation