Risk-Based Therapy for Localized Osteosarcoma.
BACKGROUND
The outcome of localized osteosarcoma has remained constant over the past 30 years. Histological response to preoperative chemotherapy is the best predictor of outcome. Strategies to alter treatment based on histological response have not resulted in increased survival.


METHODS
Patients with localized osteosarcoma received preoperative chemotherapy with cisplatin, doxorubicin, and methotrexate. Patients whose tumors had a good histological response (≥90% necrosis) continued with the same treatment postoperatively. Patients with poor histological response (<90% necrosis) received three courses of melphalan 100 mg/m(2) on day -4, cyclophosphamide 2,000 mg/m(2) on days -3, and -2 followed by stem cell infusion.


RESULTS
Fifty-two patients were enrolled. Median age was 14 years, and 56% of patients were male. The femur was the most common site. Forty patients underwent limb salvage surgery and amputation was performed in six patients. Forty-eight percent of tumors showed good histological response. Forty patients were evaluable for outcome; 18 patients with poor histologic response received high-dose chemotherapy. The 5-year event-free survival (EFS) and overall survival (OS) for patients treated on the high-dose chemotherapy arm were 28% (95% confidence interval [CI], 10-49) and 48% (95% CI, 23-69), respectively. The 5-year EFS and OS for patients treated on the standard chemotherapy arm were 62% (95% CI, 36-80) and 74% (95% CI, 44-90), respectively. All patients who received high-dose chemotherapy developed grade 3 or higher hematological toxicity. There were no treatment-related deaths.


CONCLUSIONS
Postoperative alkylator intensification with high-dose cyclophosphamide and melphalan in patients with localized osteosarcoma with poor histological response failed to improve survival.
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas.
Rajkumar
R
Venkatramani
Cook Children's Medical Center, Fort Worth, Texas.
Jeffrey
J
Murray
National Institutes of Health Clinical Center, Pediatric Oncology Branch, Bethesda, Maryland.
Lee
L
Helman
Department of Pediatrics, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma.
William
W
Meyer
Department of Pathology and Immunology and Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
M John
MJ
Hicks
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas.
Robert
R
Krance
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas.
Ching
C
Lau
Biostatistics and Informatics Shared Resource, The Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.
Eunji
E
Jo
Department of Pediatrics, Baylor College of Medicine, Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas.
Murali
M
Chintagumpala
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000628:therapy; D006801:Humans; D008297:Male; D008558:Melphalan; D008727:Methotrexate / Q000008:administration & dosage; D012516:Osteosarcoma / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D033581:Stem Cell Transplantation; D016896:Treatment Outcome
D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin; D008558:Melphalan; D008727:Methotrexate
clinical trials; high-dose chemotherapy; necrosis; osteosarcoma; stem cell transplantation