Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide.
OBJECTIVE
Standard multiagent chemotherapy for osteosarcoma may include platinum compounds, doxorubicin, and high-dose methotrexate. By identifying new chemotherapeutic strategies, the outcome of these patients can be improved and the toxicity of treatment regimens decreased.


METHODS
The authors evaluated the activity of the combination of cyclophosphamide (500 mg/m2 per day for 5 days) and etoposide (100 mg/m2 per day for 5 days) given with granulocyte colony-stimulating factor (G-CSF) to children with osteosarcoma unresponsive to conventional treatment.


RESULTS
Fourteen patients with refractory osteosarcoma were treated with this combination. Twelve patients had been previously treated with a multiagent regimen that included carboplatin, ifosfamide, methotrexate, and doxorubicin. Seven of 11 evaluable patients had a poor histologic response in their primary tumor at the time of definitive surgery (Huvos grade 1 or 2). Sites of relapse included lung, bone, and brain. A total of 47 courses were given. An overall response rate of 28.5% was achieved. A complete response was obtained in one patient (7.1%), a partial response was obtained in three patients (21.4%), and stable disease for 1 to 4 months was achieved in five patients (35.7%). Five patients (35.7%) had progressive disease. Grade 4 neutropenia was the primary form of toxicity observed; the median duration of absolute neurophil count less than 500/microL was 4 days.


CONCLUSIONS
The combination of cyclophosphamide and etoposide resulted in a response rate of 28.5% in patients with refractory or relapsed osteosarcoma, and its incorporation into front-line therapies deserves further evaluation.
Rodríguez-Galindo
Carlos
C
Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA. carlos.rodriguez-galindo@stjude.org
Daw
Najat C
NC
Kaste
Sue C
SC
Meyer
William H
WH
Dome
Jeffrey S
JS
Pappo
Alberto S
AS
Rao
Bhaskar N
BN
Pratt
Charles B
CB
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002648:Child; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D012516:Osteosarcoma / Q000188:drug therapy*; D012189:Retrospective Studies; D015996:Survival Rate; D016896:Treatment Outcome
D005047:Etoposide; D003520:Cyclophosphamide