Motoaki Chin1, Ryohei Yokoyama2, Minako Sumi3, Hajime Okita4, Akira Kawai5, Ako Hosono6, Yuhki Koga7, Hideki Sano8, Hiroyoshi Watanabe9, Toshifumi Ozaki10, Hideo Mugishima11. 1. Department of Pediatrics, Nihon University School of Medicine, Tokyo, Japan. 2. Department of Orthopedic Surgery, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan. 3. Cancer Institute Hospital-JFCR, Tokyo, Japan. 4. Department of Pathology, Keio University School of Medicine, Tokyo, Japan. 5. Department of Musculoskeletal Oncology and Rehabilitation Medicine, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Pediatric Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 7. Department of Pediatric Medicine for Hospital Collaboration, Graduate School of Medical, Sciences, Kyushu University, Fukuoka, Japan. 8. Department of Pediatric Oncology, Fukushima Medical University Hospital, Fukushima, Japan. 9. Department of Pediatrics Graduate School of Medical Sciences, Tokushima University, Tokushima, Japan. 10. Department of Orthopedic Surgery, Okayama University Hospital, Okayama, Japan. 11. Kawagoe Preventive Medical Center Clinic, Saitama, Japan.
Abstract
BACKGROUND: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT. PROCEDURE: Patients with ESFT aged < 30 years were eligible for participation. The chemotherapy regimen consisted of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) repeating every 21 days for 52 weeks. Local treatment included surgery and/or radiation therapy (0-55.8 Gy) based on the margin of resection and histologic response. The primary endpoint was progression-free survival (PFS) at three years. The study was designed to test whether the lower limit of the 90% confidence interval for PFS would exceed the threshold of 60%. The planned sample size was 53 patients, allowing for 10% of patients being ineligible. RESULTS: Of the 53 patients screened for entry, seven were deemed ineligible. Forty-six patients were considered as the per-protocol set and were used for the efficacy analysis. Three-year PFS was 71.7% (0.59-0.81). Estimated five-year PFS and overall survival were both 69.6%. Although no previously unknown adverse event was reported, three patients developed secondary malignancies (acute lymphoblastic leukemia, myelodysplastic syndrome, and osteosarcoma, one patient each). CONCLUSIONS: Multimodal treatment with standard VDC-IE chemotherapy improved the prognosis for patients with ESFT in Japan, although statistical confirmation of efficacy compared to historical control was not achieved.
BACKGROUND: The survival rate in patients with Ewing sarcoma family of tumors (ESFT) in Japan was reported to be < 50% in the 1990s. The Japan Ewing Sarcoma Study Group was established to improve the prognosis of ESFT in Japan. The aim of this phase II trial was to determine the efficacy and safety of multimodal treatment for nonmetastatic ESFT. PROCEDURE: Patients with ESFT aged < 30 years were eligible for participation. The chemotherapy regimen consisted of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) repeating every 21 days for 52 weeks. Local treatment included surgery and/or radiation therapy (0-55.8 Gy) based on the margin of resection and histologic response. The primary endpoint was progression-free survival (PFS) at three years. The study was designed to test whether the lower limit of the 90% confidence interval for PFS would exceed the threshold of 60%. The planned sample size was 53 patients, allowing for 10% of patients being ineligible. RESULTS: Of the 53 patients screened for entry, seven were deemed ineligible. Forty-six patients were considered as the per-protocol set and were used for the efficacy analysis. Three-year PFS was 71.7% (0.59-0.81). Estimated five-year PFS and overall survival were both 69.6%. Although no previously unknown adverse event was reported, three patients developed secondary malignancies (acute lymphoblastic leukemia, myelodysplastic syndrome, and osteosarcoma, one patient each). CONCLUSIONS: Multimodal treatment with standard VDC-IE chemotherapy improved the prognosis for patients with ESFT in Japan, although statistical confirmation of efficacy compared to historical control was not achieved.
Keywords:
Ewing sarcoma family of tumors; The Japan Ewing Sarcoma Study Group (JESS); multimodal treatment; progression-free survival secondary malignancies